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BackgroundIt is known that the misuse and overuse of antimicrobials leads to antimicrobial resistance (AMR). Effective communication between dispensers and users is thus crucial in reducing inappropriate antibiotic use.ObjectiveThis study aims to gain a better understanding of communication around the use of antibiotics in the community and seeks potential implementation strategies to change dispenser and user practices in communication aspects.MethodsQualitative methods were employed, including in-depth interviews with 18 drug suppliers and 16 community members, and eight focus group discussions with key informants. Data were collected in the Kanchanaburi Demographic Health Surveillance System in urban and semi-urban communities in the western region of Thailand. The thematic analysis included communication quality, communication and imbalanced power, and misconceptions and instruction. The OpenCode qualitative software program was employed.ResultsThe study revealed that the quality of communication was significantly influenced by the interaction of antibiotic dispensing with language and information. This interaction creates communication constraints between those dispensing antibiotics and the recipients, resulting in a less-than-optimal exchange of information. Consequently, users received limited information concerning the proper use of antibiotics. Furthermore, power imbalances and communication dynamics were perpetuated, mainly stemming from varying levels of access to and knowledge about antibiotics. This imbalance in power dynamics became evident between those dispensing antibiotics and the users. Users, as well as dispensers lacking proper qualifications, found themselves in a precarious position due to their inadequate knowledge of antibiotics. Moreover, it is noteworthy that misconceptions often conflicted with antibiotic instructions, leading to challenges in adhering to antibiotic regimens. These challenges primarily arose from misconceptions about antibiotics and concerns about potential side effects, particularly when users started to feel better.ConclusionsThe findings highlight the importance of enhancing communication between dispensers and users through future interventions. These interventions should aim to bolster user understanding of antibiotics and provide clear, trustworthy instructions for their proper usage. Investigating innovative communication methods, such as the use of QR codes, presents a promising avenue for consideration. By addressing these communication gaps, we can advocate for the appropriate utilization of antibiotics and mitigate the prevalence of AMR.

[This corrects the article DOI: 10.1371/journal.pone.0269385.].

Abstract Knowledge about contagiousness is key to accurate management of hospitalized COVID-19 patients. Epidemiological studies suggest that in addition to transmission through droplets, aerogenic SARS-CoV-2 transmission contributes to the spread of infection. However, the presence of virus in exhaled air has not yet been sufficiently demonstrated. In pandemic situations low tech disposable and user-friendly bedside devices are required, while commercially available samplers are unsuitable for application in patients with respiratory distress. We included 49 hospitalized COVID-19 patients and used a disposable modular breath sampler to measure SARS-CoV-2 RNA load in exhaled air samples and compared these to SARS-CoV-2 RNA load of combined nasopharyngeal throat swabs and saliva. Exhaled air sampling using the modular breath sampler has proven feasible in a clinical COVID-19 setting and demonstrated viral detection in 25% of the patients.

Abstract Background Antibiotic consumption is increasing worldwide, particularly in low and middle-income countries (LMICs). Access to lifesaving antibiotics in LMICs is crucial while minimising inappropriate use. Studies assessing the economic impact of inappropriate antibiotic use in LMICs are lacking. We explored the economic impact of inappropriate antibiotic use using the example of upper respiratory tract infections (URIs) in Ghana, as part of the ABACUS (AntiBiotic ACcess and USe) project. Methods A top-down, retrospective economic impact analysis of inappropriate antibiotic use for URIs was conducted. Two inappropriate antibiotic use situations were considered: (1) URIs treated with antibiotics, against recommendations from clinical guidelines; and (2) URIs that should have been treated with antibiotics according to clinical guidelines, but were not. The analysis included data collected in Ghana during the ABACUS project (household surveys and exit-interviews among consumers buying antibiotics), scientific literature and stakeholder consultations. Included cost types related to health care seeking behaviour for URIs. Additionally, cost saving projections were computed based on potential effects of future interventions that improve antibiotic use. Results Health care costs related to inappropriate antibiotic use for URIs were estimated to be around 20 million (M) USD annually, including 18 M USD for situation 1 and 2 M USD for situation 2. Travel costs and lost income due to travel, together, were estimated to be around 44 M USD for situation 1 and 18 M USD for situation 2. Possible health care cost savings range from 2 to 12 M USD for situation 1 and from 0.2 to 1 M USD for situation 2. Conclusions This study indicates that inappropriate antibiotic use leads to substantial economic costs in a LMIC setting that could have been prevented. We recommend investment in novel strategies to counter these unnecessary expenditures. As the projections indicate, this may result in considerable cost reductions. By tackling inappropriate use, progress can be made in combatting antibiotic resistance.

BackgroundCoronavirus disease 2019 (COVID-19) has been especially dangerous for elderly people. To reduce the risk of transmission from healthcare workers to elderly people, it is of utmost importance to detect possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive healthcare workers as early as possible. We aimed to determine whether the Abbott Panbio™ COVID-19 antigen detection rapid diagnostic test (Ag-RDT) could be used as an alternative to reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The second aim was to compare the cycle threshold (Ct) in RT-qPCR with the results of the Ag-RDT.MethodsA prospective diagnostic evaluation of the Abbott Panbio™ COVID-19 Ag-RDT among healthcare workers across three elderly care facilities as well as home-based elderly care workers who met clinical criteria for COVID-19 during the second wave of the COVID-19 pandemic. Per healthcare worker, the first nasopharyngeal swab was obtained to perform the Ag-RDT and the second swab for RT-qPCR. A Ct-value of < 40 was interpreted as positive, ≥ 40 as negative.ResultsA total of 683 healthcare workers with COVID-19 symptoms were sampled for detection of SARS-CoV-2 by both Ag-RDT and RT-qPCR. Sixty-three healthcare workers (9.2%) tested positive for SARS-CoV-2 by RT-qPCR. The overall sensitivity of Ag-RDT was 81.0% sensitivity (95%CI: 69.6-88.8%) and 100% specificity (95%CI: 99.4-100%). Using a cut-off Ct-value of 32, the sensitivity increased to 92.7% (95% CI: 82.7-97.1%). Negative Ag-RDT results were moderately associated with higher Ct-values (r = 0.62) compared to positive Ag-RDT results.ConclusionThe Panbio™ COVID-19 Ag-RDT can be used to quickly detect positive SARS-CoV-2 healthcare workers. Negative Ag-RDT should be confirmed by RT-qPCR. In case of severe understaffing and with careful consideration, fully vaccinated healthcare workers with Ag-RDT negative results could work with a mask pending PCR results.

Abstract Pediatric community-acquired bloodstream infections (CA-BSIs) in sub Saharan African humanitarian contexts are rarely documented. Effective treatment of these infections is additionally complicated by increasing rates of antimicrobial resistance. We describe the findings from epidemiological and microbiological surveillance implemented in pediatric patients with suspected CA-BSIs presenting for care at a secondary hospital in the conflict affected area of Zamfara state, Nigeria. Any child (> 2 months of age) presenting to Anka General Hospital from November 2018 to August 2020 with clinical severe sepsis at admission had clinical and epidemiological information and a blood culture collected at admission. Bacterial isolates were tested for antibiotic susceptibility. We calculated frequencies of epidemiological, microbiological and clinical parameters. We explored risk factors for death amongst severe sepsis cases using univariable and multivariable Poisson regression, adjusting for time between admission and hospital exit. We included 234 severe sepsis patients with 195 blood culture results. There were 39 positive blood cultures. Of the bacterial isolates, 14 were Gram positive and 18 were Gram negative; 5 were resistant to empiric antibiotics: methicillin-resistant Staphylococcus aureus (MRSA; n = 2) and Extended Spectrum Beta-Lactamase positive enterobacterales (n = 3). We identified no significant association between sex, age-group, ward, CA-BSI, appropriate intravenous antibiotic, malaria positivity at admission, suspected focus of sepsis, clinical severity and death in the multivariable regression. There is an urgent need for access to good clinical microbiological services, including point of care methods, and awareness and practice around rational antibiotic in healthcare staff in humanitarian settings to reduce morbidity and mortality from sepsis in children.

Objectives: We analysed the concordance of rectal swab isolates and blood culture for Gram-negative bacteria (GNB) isolates in neonates with a suspicion of neonatal sepsis admitted to a neonatal care unit in Haiti. Methods: We matched pairs of blood and rectal samples taken on the date of suspected sepsis onset in the same neonate. We calculated the proportion of rectal isolates in concordance with the blood isolates by species and genus. We calculated the negative predictive value (NPV) for GNB and extended-spectrum β-lactamase (ESBL)-producing GNB for all rectal and blood isolate pairs in neonates with suspected sepsis. Results: We identified 238 blood and rectal samples pairs, with 238 blood isolate results and 309 rectal isolate results. The overall concordance in genus and species between blood and rectal isolates was 22.3% [95% confidence interval (CI) 17.4–28.0%] and 20.6% (95% CI 16.0–26.2%), respectively. The highest concordance between blood and rectal isolates was observed for samples with no bacterial growth (65%), followed byKlebsiella pneumoniae (18%) and Klebsiella oxytoca (12%). The NPV of detecting GNB bacterial isolates in rectal samples compared with those in blood samples was 81.6% and the NPV for ESBL-positive GNB was 92.6%. Conclusions: The NPV of rectal swab GNB isolates was high in all patient groups and was even higher for ESBL-positive GNB. Clinicians can use the results from rectal swabs when taken simultaneously with blood samples during outbreaks to inform the (de-)escalation of antibiotic therapy in those neonates that have an ongoing sepsis profile.

Abstract Background Antibiotic misuse and other types of unnecessary use of antibiotics can contribute to accelerate the process of antibiotic resistance, which is considered a global concern, mostly affecting low-and middle-income countries (LMICs). In Mozambique there is limited evidence on community knowledge and practices regarding antibiotics and antibiotic resistance. As part of the ABACUS project, this paper describes knowledge and practices of antibiotic use among the general population in the semi-rural district of Manhiça to inform evidence-based communication intervention strategies for safer antibiotic use. Methods The study was conducted in Manhiça, a semi-rural district of Southern Mozambique. Sixteen in-depth interviews and four focus group discussions (FGDs) were conducted with community members to explore lay knowledge and practices regarding antibiotics and awareness of antibiotic resistance. The qualitative data was analysed using a combination of content and thematic analysis. The SRQR guidelines for reporting qualitative studies was performed. Results Although participants did not hold any consistent knowledge of antibiotics, their visual recognition of amoxicillin (distinct red yellow capsule) was acceptable, but less so for different types and brands of antibiotics. The majority of participants were aware of the term ‘antibiotic’, yet the definition they gave was rarely backed by biomedical knowledge. Participants associated antibiotics with certain colours, shapes and health conditions. Participants reported common habits that may contribute to resistance: not buying the full course, self-medication, sharing medicines and interruption of treatment. Most had never heard of the term ‘antibiotic resistance’ but were familiar with the phenomenon. They often understood the term ‘resistance’ as treatment failure and likened ‘resistance’ to non-compliance, ineffective medication, disease resistance or to an inability of the physical body to respond to it. Conclusion There is a broad understanding of the importance of medication compliance but not specifically of antibiotic resistance. In addition, there is a recognized gap between knowledge of responsible drug compliance and actual behaviour. Future qualitative research is required to further explore what determines this behaviour. The existing ability to visually identify amoxicillin by its distinct red and yellow appearance is informative for future awareness and behavioural change campaigns that may incorporate visual aids of antibiotics.

ABSTRACT Colistin is widely used in agriculture and aquaculture as prophylaxis, particularly in Asia. Recently, mcr-1 and other mobilizable genes conferring colistin resistance have spread globally in community and hospital populations. Characterizing mcr-1 mobile genetic elements and host genetic background is important to understand the transmission of this resistance mechanism. We conducted whole-genome sequencing of 94 mcr-1-positive Escherichia coli isolates (Mcr1-Ec isolates) from human and animal feces, food, and water in a community cohort (N = 87) and from clinical specimens from a referral hospital (N = 7) in northern Vietnam. mcr-1 was plasmid-borne in 71 and chromosomally carried in 25 (2 isolates contain one copy on chromosome and one copy on a plasmid) of 94 E. coli isolates from the community and hospital settings. All seven clinical isolates carried mcr-1 on plasmids. Replicon types of mcr-1-carrying plasmids included IncI2, IncP, IncX4, and IncFIA single replicons and combinations of IncHI2, IncN, and IncX1 multireplicons. Alignment of a long-read sequence of an IncI2 plasmid from animal feces with short-read sequences of IncI2 plasmids from a healthy human, water, and hospitalized patients showed highly similar structures (query cover from 90% to 98%, overall identity of >81%). We detected the potential existence of multireplicon plasmids harboring mcr-1 regardless of sample setting, confirming 10/71 with long-read sequencing. An intact/conserved Tn6330 transposon sequence or its genetic context variants were found in 6/25 Mcr1-Ec isolates with chromosomally carried mcr-1. The dissemination of mcr-1 is facilitated by a high diversity of plasmid replicon types and a high prevalence of the chromosomal Tn6330 transposon. IMPORTANCE The article presented advances our understanding of genetic elements carrying mcr-1 in Escherichia coli in both community and hospital settings. We provide evidence to suggest that diverse plasmid types, including multireplicon plasmids, have facilitated the successful transmission of mcr-1 in different reservoirs. The widespread use of colistin in agriculture, where a high diversity of bacteria are exposed, has allowed the selection and evolution of various transmission mechanisms that will make it a challenge to get rid of. Colocalization of mcr-1 and other antibiotic resistance genes (ARGs) on multireplicon plasmids adds another layer of complexity to the rapid dissemination of mcr-1 genes among community and hospital bacterial populations and to the slow pandemic of antimicrobial resistance (AMR) in general.

In low-resource settings, detection of healthcare-acquired outbreaks in neonatal units relies on astute clinical staff to observe unusual morbidity or mortality from sepsis as microbiological diagnostics are often absent. We aimed to generate reliable (and automated) early warnings for potential clusters of neonatal late onset sepsis using retrospective data that could signal the start of an outbreak in an NCU in Port au Prince, Haiti, using routinely collected data on neonatal admissions. We constructed smoothed time series for late onset sepsis cases, late onset sepsis rates, neonatal care unit (NCU) mortality, maternal admissions, neonatal admissions and neonatal antibiotic consumption. An outbreak was defined as a statistical increase in any of these time series indicators. We created three outbreak alarm classes: 1) thresholds: weeks in which the late onset sepsis cases exceeded four, the late onset sepsis rates exceeded 10% of total NCU admissions and the NCU mortality exceeded 15%; 2) differential: late onset sepsis rates and NCU mortality were double the previous week; and 3) aberration: using the improved Farrington model for late onset sepsis rates and NCU mortality. We validated pairs of alarms by calculating the sensitivity and specificity of the weeks in which each alarm was launched and comparing each alarm to the weeks in which a single GNB positive blood culture was reported from a neonate. The threshold and aberration alarms were the strongest predictors for current and future NCU mortality and current LOS rates (p

Abstract Background As in many other low and middle income countries (LIMCs), Vietnam has experienced a major growth in the pharmaceutical industry, with large numbers of pharmacies and drug stores, and increasing drug expenditure per capita over the past decade. Despite regulatory frameworks that have been introduced to control the dispensing and use of prescription-only drugs, including antibiotics, compliance has been reported to be strikingly low particularly in rural parts of Vietnam. This qualitative study aimed to understand antibiotic access and use practices in the community from both supplier and consumer perspectives in order to support the identification and development of future interventions. Methods This qualitative study was part of a project on community antibiotic access and use (ABACUS) in six LMICs. The focus was Ba Vi district of Hanoi capital city, where we conducted 16 indepth interviews (IDIs) with drug suppliers, and 16 IDIs and 6 focus group discussions (FGDs) with community members. Drug suppliers were sampled based on mapping of all informal and formal antibiotic purchase or dispensing points in the study area. Community members were identified through local networks and relationships with the field collaborators. All IDIs and FGDs were audio-taped, transcribed and analysed using content analysis. Results We identified a large number of antibiotic suppliers in the locality with widespread infringements of regulatory requirements. Established reciprocal relationships between suppliers and consumers in drug transactions were noted, as was the consumers’ trust in the knowledge and services provided by the suppliers. In addition, antibiotic use has become a habitual choice in most illness conditions, driven by both suppliers and consumers. Conclusions This study presents an analysis of the practices of antibiotic access and use in a rural Vietnamese setting. It highlights the interactions between antibiotic suppliers and consumers in the community and identifies possible targets for interventions.

Abstract Background ‘Yaa Chud’ is a non-prescribed poly-pharmaceutical pack containing several types of drugs, including antibiotics and steroids, which can be purchased over the counter in Thailand for self-medication. Although it is illegal, it is still available at some community outlets. This study aimed to understand access to and use of Yaa Chud at the community level in order to raise awareness on its usage and to provide policy recommendations to address the problem. Methods This study employed qualitative methods, including in-depth interviews with 18 drug suppliers and 16 community members, and six focus group discussions. It included inventories from 17 drug suppliers. Data were collected in selected communities of the Kanchanaburi Demographic Surveillance System, located in the western region of Thailand.Thematic analysis was based upon the Health Services Utilization Model and conducted using the Open Code qualitative software program. Results Overcrowding, long waiting times, and a perceived unwelcoming environment at public health-care service outlets were identified as factors that drive people into the private sector, where loose regulation of drug laws facilitates access and use of Yaa Chud. Migrants and older people were most likely to seek and use Yaa Chud, especially for mild illness. Availability, easy access through a user’s network, low cost, and perceived effectiveness were identified as factors that enable access and use of Yaa Chud. Conclusions Though illegal in Thailand, Yaa Chud is likely to remain available for self-medication by community members, due to the persisting demand by the elderly and migrant workers. There is an urgent need to replace these mixed medications with better choices. Safer Yaa Chud may be a preferred, first-line health-care option, which could help reduce congestion in the formal health-care setting. At the same time, enforcement of regulatory compliance needs to be continued in order to stop the supply of unsafe Yaa Chud.

Summary: Handheld Electronic Devices (HEDs) play a central role in the hospital environment. However, they can be a vehicle for transmitting (pathogenic) microorganisms. We studied whether disinfection with UV-C light is successful in disinfecting three different HEDs in a clinical setting. Disinfection with UV-C light was performed with the UV-Smart® D25. We took a total of 800 samples on two departments and counted colony forming units. More than half of the baseline measurements were moderately (>10CFU) or highly (>50 CFU) contaminated. Post-disinfection the CFU was 0 in 87% of measurements. We conclude that the UV-Smart® D25 can be used to disinfect non-critical HEDs in clinical healthcare.

BackgroundNew hemocytometric parameters can be used to differentiate causes of acute febrile illness (AFI). We evaluated a software algorithm-Infection Manager System (IMS)-which uses hemocytometric data generated by Sysmex hematology analyzers, for its accuracy to detect bacteremia in AFI patients with and without malaria in Burkina Faso. Secondary aims included comparing the accuracy of IMS with C-reactive protein (CRP) and procalcitonin (PCT).MethodsIn a prospective observational study, patients of ≥ three-month-old (range 3 months- 90 years) presenting with AFI were enrolled. IMS, blood culture and malaria diagnostics were done upon inclusion and additional diagnostics on clinical indication. CRP, PCT, viral multiplex PCR on nasopharyngeal swabs and bacterial- and malaria PCR were batch-tested retrospectively. Diagnostic classification was done retrospectively using all available data except IMS, CRP and PCT results.FindingsA diagnosis was affirmed in 549/914 (60.1%) patients and included malaria (n = 191) bacteremia (n = 69), viral infections (n = 145), and malaria-bacteremia co-infections (n = 47). The overall sensitivity, specificity, and negative predictive value (NPV) of IMS for detection of bacteremia in patients of ≥ 5 years were 97.0% (95% CI: 89.8-99.6), 68.2% (95% CI: 55.6-79.1) and 95.7% (95% CI: 85.5-99.5) respectively, compared to 93.9% (95% CI: 85.2-98.3), 39.4% (95% CI: 27.6-52.2), and 86.7% (95% CI: 69.3-96.2) for CRP at ≥20mg/L. The sensitivity, specificity and NPV of PCT at 0.5 ng/ml were lower at respectively 72.7% (95% CI: 60.4-83.0), 50.0% (95% CI: 37.4-62.6) and 64.7% (95% CI: 50.1-77.6) The diagnostic accuracy of IMS was lower among malaria cases and patients InterpretationIMS is a new diagnostic tool to differentiate causes of AFI. Its high NPV for bacteremia has the potential to improve antibiotic dispensing practices in healthcare facilities with hematology analyzers. Future studies are needed to evaluate whether IMS, combined with malaria diagnostics, may be used to rationalize antimicrobial prescription in malaria endemic areas.Trial registrationClinicalTrials.gov (NCT02669823) https://clinicaltrials.gov/ct2/show/NCT02669823.

Background Antibiotic resistance poses a great threat to global health, especially in low- and middle-income countries with a high infectious disease burden and limited resources. In spite of regulations, antibiotics are sold in many settings as non-prescription medicines, resulting in inappropriate use and resistance. Objective This study aimed to investigate the current status of access and use of antibiotics in rural Bangladesh, by exploring the perspectives and sales practices of antibiotic drug dispensers. Methods We used a mixed methods approach (qualitative and quantitative). We mapped and characterized antibiotic purchasing and dispensing sites in the Matlab Health and Demographic Surveillance System catchment area. Furthermore, we investigated the volume of provision of systemic antibiotics in 10 drug outlets. We held 16 in-depth interviews with randomly selected antibiotics dispensers. Interviews explored factors associated with antibiotic selling. Responses were transcribed, coded for themes, and summarized. We used ATLAS.ti 5.2 for conducting a thematic analysis. Results A total of 301 antibiotic dispensers were identified, of whom 92% (n = 278) were private and 8% (n = 23) public. 52% (n = 155) operated informally (i.e. without legal authorization). In order to promote and survive in their business, dispensers sell antibiotics for a range of conditions without a qualified physician’s prescription. Factors that facilitate these inappropriate sales include lack of access to healthcare in the rural community, inadequate doctor: population ratio, limited dispenser knowledge, poor pharmacovigilance concerning safety of self medication, lack of enforcement of policies, financial benefits for both customers and dispensers, and high dependency on pharmaceutical companies’ information. Conclusion Dispensers in rural Bangladesh sell antibiotics inappropriately by ignoring existing national regulations. They operate the antibiotic sales without facing any legal barriers and primarily with a view to sustain their business, resulting in inappropriate sales of antibiotics to the rural community. The influence of the drug industry needs to be replaced with evidence-based, not commercially driven information. Awareness programs for antibiotic providers that promote understanding of antibiotics and antibiotic resistance through tailored interventions may be helpful in changing current antibiotic sales practices.

Antimicrobial stewardship (AMS) is a set of coordinated strategies to improve the use of antimicrobials, to enhance patient outcomes, reduce antimicrobial resistance, and decrease unnecessary costs. The pioneer years of AMS were restricted to high-income countries (HIC), where overconsumption of antibiotics was associated with emergence of multidrug-resistant (MDR) bacteria. AMS in low- and middle-income countries (LMIC) is also necessary. However, programs effective in HIC may not perform as well in LMIC, because (i) While decreased consumption of antibiotics may be an appropriate target in overconsuming HIC, this may be dangerous in LMIC, where many patients die from the lack of access to antibiotics; (ii) although AMS programs in HIC can be designed and monitored through laboratory surveillance of resistance, surveillance programs are not available in many LMIC; (iii) the heterogeneity of health care systems implies that AMS programs must be carefully contextualized. Despite the need to individually tailor AMS programs in LMIC, international collaborations remain highly valuable, through the dissemination of high-quality documents and educational material, that may be shared, adapted where needed, and adopted worldwide. This process, facilitated by modern communication tools, combines many benefits, including: (i) saving time, a precious dimension for health care workers, by avoiding the duplication of similar works in different settings; (ii) taking advantage of colleagues skills, and initiatives, through open access to the work performed in other parts of the world; (iii) sharing experiences, so that we all learn from each others' successes and failures.

Abstract Background Antimicrobial resistance (AMR) poses a colossal threat to global health and incurs high economic costs to society. Economic evaluations of antimicrobials and interventions such as diagnostics and vaccines that affect their consumption rarely include the costs of AMR, resulting in sub-optimal policy recommendations. We estimate the economic cost of AMR per antibiotic consumed, stratified by drug class and national income level. Methods The model is comprised of three components: correlation coefficients between human antibiotic consumption and subsequent resistance; the economic costs of AMR for five key pathogens; and consumption data for antibiotic classes driving resistance in these organisms. These were used to calculate the economic cost of AMR per antibiotic consumed for different drug classes, using data from Thailand and the United States (US) to represent low/middle and high-income countries. Results The correlation coefficients between consumption of antibiotics that drive resistance in S. aureus, E. coli, K. pneumoniae, A. baumanii, and P. aeruginosa and resistance rates were 0.37, 0.27, 0.35, 0.45, and 0.52, respectively. The total economic cost of AMR due to resistance in these five pathogens was $0.5 billion and $2.9 billion in Thailand and the US, respectively. The cost of AMR associated with the consumption of one standard unit (SU) of antibiotics ranged from $0.1 for macrolides to $0.7 for quinolones, cephalosporins and broad-spectrum penicillins in the Thai context. In the US context, the cost of AMR per SU of antibiotic consumed ranged from $0.1 for carbapenems to $0.6 for quinolones, cephalosporins and broad spectrum penicillins. Conclusion The economic costs of AMR per antibiotic consumed were considerable, often exceeding their purchase cost. Differences between Thailand and the US were apparent, corresponding with variation in the overall burden of AMR and relative prevalence of different pathogens. Notwithstanding their limitations, use of these estimates in economic evaluations can make better-informed policy recommendations regarding interventions that affect antimicrobial consumption and those aimed specifically at reducing the burden of AMR.

Abstract Background Sinks in patient rooms are associated with hospital-acquired infections. The aim of this study was to evaluate the effect of removal of sinks from the Intensive Care Unit (ICU) patient rooms and the introduction of ‘water-free’ patient care on gram-negative bacilli colonization rates. Methods We conducted a 2-year pre/post quasi-experimental study that compared monthly gram-negative bacilli colonization rates pre- and post-intervention using segmented regression analysis of interrupted time series data. Five ICUs of a tertiary care medical center were included. Participants were all patients of 18 years and older admitted to our ICUs for at least 48 h who also received selective digestive tract decontamination during the twelve month pre-intervention or the twelve month post-intervention period. The effect of sink removal and the introduction of ‘water-free’ patient care on colonization rates with gram-negative bacilli was evaluated. The main outcome of this study was the monthly colonization rate with gram-negative bacilli (GNB). Yeast colonization rates were used as a ‘negative control’. In addition, colonization rates were calculated for first positive culture results from cultures taken ≥3, ≥5, ≥7, ≥10 and ≥14 days after ICU-admission, rate ratios (RR) were calculated and differences tested with chi-squared tests. Results In the pre-intervention period, 1496 patients (9153 admission days) and in the post-intervention period 1444 patients (9044 admission days) were included. Segmented regression analysis showed that the intervention was followed by a statistically significant immediate reduction in GNB colonization in absence of a pre or post intervention trend in GNB colonization. The overall GNB colonization rate dropped from 26.3 to 21.6 GNB/1000 ICU admission days (colonization rate ratio 0.82; 95%CI 0.67–0.99; P = 0.02). The reduction in GNB colonization rate became more pronounced in patients with a longer ICU-Length of Stay (LOS): from a 1.22-fold reduction (≥2 days), to a 1.6-fold (≥5 days; P = 0.002), 2.5-fold (for ≥10 days; P

Background The use of large quantities of antimicrobial drugs for human health and agriculture is advancing the predominance of drug resistant pathogens in the environment. Antimicrobial resistance is now a major public health threat posing significant challenges for achieving the Sustainable Development Goals. In Bangladesh, where over one third of the population is below the poverty line, the achievement of safe and effective antibiotic medication use for human health is challenging. Objective To explore factors and practices around access and use of antibiotics and understanding of antimicrobial resistance in rural communities in Bangladesh from a socio-cultural perspective. Methods This qualitative study comprises the second phase of the multi-country ABACUS (Antibiotic Access and Use) project in Matlab, Bangladesh. Information was collected through six focus group discussions and 16 in-depth interviews. Informants were selected from ten villages in four geographic locations using the Health and Demographic Surveillance System database. The Access to Healthcare Framework guided the interpretation and framing of the findings in terms of individuals’ abilities to: perceive, seek, reach, pay and engage with healthcare. Results Village pharmacies were the preferred and trusted source of antibiotics for self-treatment. Cultural and religious beliefs informed the use of herbal and other complementary medicines. Advice on antibiotic use was also sourced from trusted friends and family members. Access to government-run facilities required travel on poorly maintained roads. Reports of structural corruption, stock-outs and patient safety risks eroded trust in the public sector. Some expressed a willingness to learn about antibiotic resistance. Conclusion Antimicrobial resistance is both a health and development issue. Social and economic contexts shape medicine seeking, use and behaviours. Multi-sectoral action is needed to confront the underlying social, economic, cultural and political drivers that impact on the access and use of antibiotic medicines in Bangladesh.

Introduction Low-income and middle-income countries (LMICs) are crucial in the global response to antimicrobial resistance (AMR), but diverse health systems, healthcare practices and cultural conceptions of medicine can complicate global education and awareness-raising campaigns. Social research can help understand LMIC contexts but remains under-represented in AMR research.Objective To (1) Describe antibiotic-related knowledge, attitudes and practices of the general population in two LMICs. (2) Assess the role of antibiotic-related knowledge and attitudes on antibiotic access from different types of healthcare providers.Design Observational study: cross-sectional rural health behaviour survey, representative of the population level.Setting General rural population in Chiang Rai (Thailand) and Salavan (Lao PDR), surveyed between November 2017 and May 2018.Participants 2141 adult members (≥18 years) of the general rural population, representing 712 000 villagers.Outcome measures Antibiotic-related knowledge, attitudes and practices across sites and healthcare access channels.Findings Villagers were aware of antibiotics (Chiang Rai: 95.7%; Salavan: 86.4%; p

Background In Ghana, there is extensive over-the-counter dispensing of antibiotics, resulting in high levels of inappropriate use, and an increase in antibiotic resistance. Regulations prevent Licenced Chemical Sellers (LCS, Over-the-Counter Medicine Sellers) from selling antibiotics other than Cotrimoxazole. In practice, however, these sellers sell a variety of antibiotics. This paper aims to provide insight into the differences between regulatory and community demands on the sale of antibiotics, and to explore how these differences in demand could be resolved to facilitate safe and appropriate use of antibiotics in rural Ghana. Methods A total of 32 in-depth interviews were conducted in the Kintampo North and South Districts in Ghana; 16 among antibiotic suppliers, predominantly LCS, and 16 among community members. Six focus group discussions were also conducted among 40 community members. Data were coded using Nvivo 10 and thematically analyzed in line with study objectives. The results are presented as narratives with quotes to illustrate the findings. Results Generally, antibiotic suppliers were aware that regulations prevent LCS from selling antibiotics except Cotrimoxazole. However, LCS sell all types of antibiotics because of community demand, economic motivations of LCS, and the poor implementation of regulations that are intended to prevent them from selling these medications. Factors that influence community demand for antibiotics include previous knowledge of effectiveness of some antibiotics, delays in seeking care at health facilities, financial constraints, and distance to health facilities. LCS suggested that they should be trained and allowed to sell some types of antibiotics instead of being prevented completely from selling. Community members also suggested that Community-based Health Planning and Services (CHPS) compounds should be equipped to dispense antibiotics. Conclusion The sale of antibiotics by LCS at the community level is influenced by both structural and individual contextual factors. There is a need to educate community members on the appropriate access and use of antibiotics in rural Ghana. In addition, rather than enforcing rules that go against practice, it may be more effective to regulate the sale of antibiotics by LCS and train them to make their dispensing more appropriate. CHPS compound could also be equipped to dispense some antibiotics to improve appropriate antibiotic access at the community level.

Burkholderia pseudomallei, a Tier 1 Select Agent and the cause of melioidosis, is a Gram-negative bacillus present in the environment in many tropical countries. Defining the global pattern of B. pseudomallei distribution underpins efforts to prevent infection, and is dependent upon robust environmental sampling methodology. Our objective was to review the literature on the detection of environmental B. pseudomallei, update the risk map for melioidosis, and propose international consensus guidelines for soil sampling.An international working party (Detection of Environmental Burkholderia pseudomallei Working Party (DEBWorP)) was formed during the VIth World Melioidosis Congress in 2010. PubMed (January 1912 to December 2011) was searched using the following MeSH terms: pseudomallei or melioidosis. Bibliographies were hand-searched for secondary references. The reported geographical distribution of B. pseudomallei in the environment was mapped and categorized as definite, probable, or possible. The methodology used for detecting environmental B. pseudomallei was extracted and collated. We found that global coverage was patchy, with a lack of studies in many areas where melioidosis is suspected to occur. The sampling strategies and bacterial identification methods used were highly variable, and not all were robust. We developed consensus guidelines with the goals of reducing the probability of false-negative results, and the provision of affordable and 'low-tech' methodology that is applicable in both developed and developing countries.The proposed consensus guidelines provide the basis for the development of an accurate and comprehensive global map of environmental B. pseudomallei.

BACKGROUND:The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam. METHODS AND FINDINGS:Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008-2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS

Microscopic [corrected] Observation Drug Susceptibility (MODS) has been shown to be an effective and rapid technique for early diagnosis of tuberculosis (TB). Thus far only a limited number of studies evaluating MODS have been performed in children and in extra-pulmonary tuberculosis. This study aims to assess relative accuracy and time to positive culture of MODS for TB diagnosis in children admitted to a general pediatric hospital in Vietnam.Specimens from children with suspected TB were tested by smear, MODS and Lowenstein-Jensen agar (LJ). 1129 samples from 705 children were analyzed, including sputum (n=59), gastric aspirate (n=775), CSF (n=148), pleural fluid (n=33), BAL (n=41), tracheal fluid (n=45), other (n=28). 113 TB cases were defined based on the "clinical diagnosis" (confirmed and probable groups) as the reference standard, in which 26% (n=30) were diagnosed as extra-pulmonary TB. Analysis by patient shows that the overall sensitivity and specificity of smear, LJ and MODS against "clinical diagnosis" was 8.8% and 100%, 38.9% and 100%, 46% and 99.5% respectively with MODS significantly more sensitive than LJ culture (P=0.02). When analyzed by sample type, the sensitivity of MODS was significantly higher than LJ for gastric aspirates (P=0.004). The time to detection was also significantly shorter for MODS than LJ (7 days versus 32 days, P

Molecular genetic approaches typically detect recombination in microbes regardless of assumed asexuality. However, genetic data have shown the AIDS-associated pathogen Penicillium marneffei to have extensive spatial genetic structure at local and regional scales, and although there has been some genetic evidence that a sexual cycle is possible, this haploid fungus is thought to be genetically, as well as morphologically, asexual in nature because of its highly clonal population structure. Here we use comparative genomics, experimental mixed-genotype infections, and population genetic data to elucidate the role of recombination in natural populations of P. marneffei. Genome wide comparisons reveal that all the genes required for meiosis are present in P. marneffei, mating type genes are arranged in a similar manner to that found in other heterothallic fungi, and there is evidence of a putatively meiosis-specific mutational process. Experiments suggest that recombination between isolates of compatible mating types may occur during mammal infection. Population genetic data from 34 isolates from bamboo rats in India, Thailand and Vietnam, and 273 isolates from humans in China, India, Thailand, and Vietnam show that recombination is most likely to occur across spatially and genetically limited distances in natural populations resulting in highly clonal population structure yet sexually reproducing populations. Predicted distributions of three different spatial genetic clusters within P. marneffei overlap with three different bamboo rat host distributions suggesting that recombination within hosts may act to maintain population barriers within P. marneffei.

OBJECTIVES:To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam. METHODS:From May 2007 to December 2008, cerebrospinal fluid (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and polymerase chain reaction targeting Neisseria meningitidis, Streptococcus pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV), Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures and clinically indicated radiology were also performed. Patients were classified as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM), neurocysticercosis and others. RESULTS:352 (male: 66%) patients were recruited: median age 34 years (range 13-85). 95/352 (27.3%) diagnoses were laboratory confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19), CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1), S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of 262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM (15.2%), AEM (10%), and BM (2.8%). CONCLUSIONS:Most infections lacked microbiological confirmation. S. suis was the most common cause of BM in this setting. Improved diagnostics are needed for meningoencephalitic syndromes to inform treatment and prevention strategies.

Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage. As a result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue.

It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection.49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC(0-12) values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC(50) (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy.

PROBLEM: Streptococcus suis is a common cause of adult bacterial meningitis in Viet Nam, and possibly other parts of Asia, yet this disabling infection has been largely neglected. Prevention, diagnosis and treatment are relatively straightforward and affordable but, in early 2007, no national diagnostic, case management or prevention guidelines existed in Viet Nam. APPROACH: Enhanced detection of S. suis infections was established in 2007 as part of a collaborative research programme between the National Hospital for Tropical Diseases, a key national hospital with very close links to the Ministry of Health, and a research group affiliated with Oxford University based in Viet Nam. The results were reported directly to policy-makers at the Ministry of Health. LOCAL SETTING: Viet Nam is a low-income country with a health-care system that has seen considerable improvements and increased autonomy. However, parts of the system remain fairly centralized the Ministry of Health. RELEVANT CHANGES: Following the improved detection and reporting of S. suis cases, the Ministry of Health issued guidance to all hospitals in Viet Nam on the clinical and laboratory diagnosis, treatment and prevention of S. suis. A public health laboratory diagnostic service was established at the National Institute of Hygiene and Epidemiology and training courses were conducted for clinicians and microbiologists. Ministry of Health guidance on surveillance and control of communicable diseases was updated to include a section on S. suis. LESSONS LEARNT: Research collaborations can efficiently inform and influence national responses if they are well positioned to reach policy-makers.