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Background: Routine microbiology results are a valuable source of antimicrobial resistance (AMR) surveillance data in low- and middle-income countries (LMICs) as well as in high-income countries. Different approaches and strategies are used to generate AMR surveillance data. Objectives: We aimed to review strategies for AMR surveillance using routine microbiology results in LMICs and to highlight areas that need support to generate high-quality AMR data. Sources: We searched PubMed for papers that used routine microbiology to describe the epidemiology of AMR and drug-resistant infections in LMICs. We also included papers that, from our perspective, were critical in highlighting the biases and challenges or employed specific strategies to overcome these in reporting AMR surveillance in LMICs. Content: Topics covered included strategies of identifying AMR cases (including case-finding based on isolates from routine diagnostic specimens and case-based surveillance of clinical syndromes), of collecting data (including cohort, point-prevalence survey, and case–control), of sampling AMR cases (including lot quality assurance surveys), and of processing and analysing data for AMR surveillance in LMICs. Implications: The various AMR surveillance strategies warrant a thorough understanding of their limitations and potential biases to ensure maximum utilization and interpretation of local routine microbiology data across time and space. For instance, surveillance using case-finding based on results from clinical diagnostic specimens is relatively easy to implement and sustain in LMIC settings, but the estimates of incidence and proportion of AMR is at risk of biases due to underuse of microbiology. Case-based surveillance of clinical syndromes generates informative statistics that can be translated to clinical practices but needs financial and technical support as well as locally tailored trainings to sustain. Innovative AMR surveillance strategies that can easily be implemented and sustained with minimal costs will be useful for improving AMR data availability and quality in LMICs.

Objectives To investigate the feasibility of retrospective prescription-based review and to describe the antibiotic prescribing patterns to provide information for an antimicrobial stewardship programme in Viet Nam Methods This study was conducted in two provincial-level hospitals between February and April 2020. Reviews were done by a clinical team consisting of leaders/senior doctors of each ward to assess the optimal level (optimal/adequate/suboptimal/inadequate/not assessable) of antibiotic prescriptions. Mixed-effect logistic regression at prescription level was used to explore factors associated with optimal antibiotic use. Results The retrospective prescription-based review was accepted by study clinical wards with varied levels of participants. One hundred and eighty-three patients (326 prescriptions) in Hospital 1 and 200 patients (344 prescriptions) in Hospital 2 were included. One hundred and nineteen of the 326 (36.5%) antibiotic prescriptions in Hospital 1 and 51/344 (14.8%) antibiotic prescriptions in Hospital 2 were determined to be optimal by the review teams. The number of adequate antibiotic prescriptions were 179/326 (54.9%) and 178 (51.7%) in Hospital 1 and Hospital 2, respectively. The optimal level was lower for surgical prophylaxis antibiotics than for empirical therapy (OR = 0.06; 95% CI 0.01–0.45), higher in prescriptions in the ICU (OR = 12.00; 95% CI 3.52–40.92), higher in definitive antibiotic therapy (OR = 48.12; 95% CI 7.17–322.57) and higher in those with an indication recorded in medical records (OR = 3.46; 95% CI 1.13–10.62). Conclusions This study provides evidence on the feasibility of retrospective prescription-based review, with adaption to the local situation. High and varying levels of optimal antibiotic prescriptions in clinical wards in hospitals were observed in Viet Nam.

Bloodstream infections (BSIs) are a leading cause of sepsis, which is a life-threatening condition that significantly contributes to the mortality of bacterial infections. Aminoglycoside antibiotics such as gentamicin or amikacin are essential medicines in the treatment of BSIs, but their clinical efficacy is increasingly being compromised by antimicrobial resistance. The aminoglycoside apramycin has demonstrated preclinical efficacy against aminoglycoside-resistant and multidrug-resistant (MDR) Gram-negative bacilli (GNB) and is currently in clinical development for the treatment of critical systemic infections.This study collected a panel of 470 MDR GNB isolates from healthcare facilities in Cambodia, Laos, Singapore, Thailand and Vietnam for a multicentre assessment of their antimicrobial susceptibility to apramycin in comparison with other aminoglycosides and colistin by broth microdilution assays.Apramycin and amikacin MICs ≤ 16 µg/mL were found for 462 (98.3%) and 408 (86.8%) GNB isolates, respectively. Susceptibility to gentamicin and tobramycin (MIC ≤ 4 µg/mL) was significantly lower at 122 (26.0%) and 101 (21.5%) susceptible isolates, respectively. Of note, all carbapenem and third-generation cephalosporin-resistant Enterobacterales, all Acinetobacter baumannii and all Pseudomonas aeruginosa isolates tested in this study appeared to be susceptible to apramycin. Of the 65 colistin-resistant isolates tested, four (6.2%) had an apramycin MIC16 µg/mL.Apramycin demonstrated best-in-class activity against a panel of GNB isolates with resistances to other aminoglycosides, carbapenems, third-generation cephalosporins and colistin, warranting continued consideration of apramycin as a drug candidate for the treatment of MDR BSIs.

BackgroundVietnam has high rates of antibiotic resistance, driven by overuse in agriculture, hospital, and community healthcare. Measures of resistance in commensal bacteria could provide a hard indicator for progress in evaluating the impact of interventions to reduce antibiotic use in the community. This study aimed to evaluate the feasibility, acceptability, and bacterial recovery for health-worker (HW) administered compared to self-administered swabs to recover Streptococcus pneumoniae, and stool collection to recover Enterobacterales in a community-based pilot study.MethodsWe conducted a cross-sectional mixed methods study in a rural community in Ha Nam Province, northern Vietnam. Between 16 July 2018 and 10 April 2019, 389 households were invited to participate in a household survey, Households were randomly selected and allocated in a 2:1 ratio to provide self-administered nasal swabs, or HW-administered nasopharyngeal swabs. Structured interviews were conducted with each household, and stool samples were self-collected from all household members. In-depth interviews with participants and health-workers were conducted in August 2018 to explore perspectives about different sample collection methods.Results324 households participated (83%), representing 1502 individuals. Stool samples were collected from 1498 individuals, self-administered nasal swabs from 1002 and HW-administered nasopharyngeal swabs from 496. S. pneumoniae were recovered from 11.1% (128/1,149) of the total population and 26.2% (48/183) of those under 5-years. Recovery was higher for HW-administered swabs (13.7%, 48/350) than self-administered swabs (10.0%, 80/799) (OR 2.06, 95% CI 1.07-3.96). Five main themes related to feasibility emerged through qualitative interviews: workload for data collectors; sample collection procedures; concerns about quality; storage and transportation; and disruptions. Nasopharyngeal swabs administered by health-workers took longer to collect, caused more discomfort and were more difficult to take from children. Costs per swab were cheaper for self-administered ($7.26) than HW-administered swabs ($8.63), but the total cost for 100 positive samples was higher ($7,260 and $6,300 respectively). Only 3 households refused to participate, representing a high acceptability of taking part. Factors affecting motivation to participate included sense of contribution, perceived trade-offs between benefits and effort, influence from others. Reluctance was related to stool sampling and negative perceptions of research. ConclusionsThis study provides important evidence for planning community-based carriage studies, including cost, logistics, and participant feedback about acceptability of different methods. Self-administered swabs had lower recovery, and though cheaper and quicker, this would translate to higher costs for large population-based studies requiring adequate numbers of positive samples for further testing. Factors that might improve recovery for self-administered swabs include swab-type, transport medium, and improved cold-chain to lab.

Background Manual blood culture bottles (BCBs) are frequently used in low-resource settings. There are few BCB performance evaluations, especially evaluations comparing them with automated systems. We evaluated two manual BCBs (Bi-State BCB and BacT/ALERT BCB) and compared their yield and time to growth detection with those of automated BacT/ALERT system. Methods BCBs were spiked in triplicate with 177 clinical isolates representing pathogens common in low-resource settings (19 bacterial and one yeast species) in adult and paediatric volumes, resulting in 1056 spiked BCBs per BCB system. Growth in manual BCBs was evaluated daily by visually inspecting the broth, agar slant, and, for BacT/ALERT BCB, colour change of the growth indicator. The primary outcomes were BCB yield (proportion of spiked BCB showing growth) and time to detection (proportion of positive BCB with growth detected on day 1 of incubation). 95% CI for yield and growth on day 1 were calculated using bootstrap method for clustered data using. Secondary outcomes were time to colony for all BCBs (defined as number of days between incubation and colony growth sufficient to use for further testing) and difference between time to detection in broth and on agar slant for the Bi-State BCBs. Findings Overall yield was 95·9% (95% CI 93·9–98·0) for Bi-State BCB and 95·5% (93·3–97·8) for manual BacT/ALERT, versus 96·1% (94·0–98·1) for the automated BacT/ALERT system (p=0·61). Day 1 growth was present in 920 (90·8%) of 1013 positive Bi-State BCB and 757 (75·0%) of 1009 positive manual BacT/ALERT BCB, versus 1008 (99·3%) of 1015 automated bottles. On day 2, detection rates were 100% for BI-State BCB, 97·7% for manual BacT/ALERT BCB, and 100% for automated bottles. For Bi-State BCB, growth mostly occurred simultaneously in broth and slant (81·7%). Sufficient colony growth on the slant to perform further tests was present in only 44·1% of biphasic bottles on day 2 and 59·0% on day 3. Interpretation The yield of manual BCB was comparable with the automated system, suggesting that manual blood culture systems are an acceptable alternative to automated systems in low-resource settings. Bi-State BCB outperformed manual BacT/ALERT bottles, but the agar slant did not allow earlier detection nor earlier colony growth. Time to detection for manual blood culture systems still lags that of automated systems, and research into innovative and affordable methods of growth detection in manual BCBs is encouraged. Funding Médecins Sans Frontières and Department of Economy, Science and Innovation of the Flemish Government.

Highlights • Antimicrobial stewardship (AMS) in low- and middle-income settings has multiple players. • Leadership commitment greatly influences AMS implementation in hospitals. • Staff showed good perception of AMS but misperceptions on local resistance levels. • Guidelines on staffing and training standards are needed to support implementation. • More support is needed to promote active roles of pharmacists and microbiologists., Objectives This study aimed to analyse the current state of antimicrobial stewardship (AMS) in hospitals in Viet Nam, a lower-middle income country (LMIC), to identify factors determining success in AMS implementation and associated challenges to inform planning and design of future programmes. Methods We conducted a mixed-methods study in seven acute-care hospitals in the antimicrobial resistance (AMR) surveillance network in Viet Nam. Data collection included 7 focus group discussions, 40 in-depth interviews and a self-administered quantitative survey of staff on AMR and AMS programmes. We summarised qualitative data by reporting the most common themes according to the core AMS elements, and analysed quantitative data using proportions and a linear mixed-effects model. Results The findings reveal a complex picture of factors and actors involved in AMS implementation from the national level to the departmental and individual level within each hospital. The level of implementation varied, starting from the formation of an AMS committee, with or without active delivery of specific interventions. Development of treatment guidelines, pre-authorisation of antimicrobial drug classes, and post-prescription audit and feedback to doctors in selected clinical departments were the main interventions reported. A higher level of leadership support and commitment to AMS led to a higher level of engagement with AMS activities from the AMS team and effective collaboration between departments involved. Conclusion Establishing country-specific guidelines on AMS staffing and adapting standards for AMS education and training from international resources are needed to support capacity building to implement AMS programmes effectively in LMICs such as Viet Nam.

BackgroundAlthough it is accepted that long-lasting insecticidal net (LLIN) use is an effective means to prevent malaria, children aged 5 to 15 years do not appear to be sufficiently protected in Madagascar; the malaria prevalence is highest in this age group. The purpose of this research is to summarize recent qualitative studies describing LLIN use among the Malagasy people with a focus on children aged 5–15 years.MethodsQualitative data from three studies on malaria conducted between 2012 and 2016 in 10 districts of Madagascar were analysed. These studies cover all malaria epidemiological profiles and 10 of the 18 existing ethnic groups in Madagascar. A thematic analysis was conducted on the collected data from semi-structured interviews, direct observation data, and informal interviews.ResultsA total of 192 semi-structured interviews were conducted. LLINs are generally perceived positively because they protect the health and well-being of users. However, regional representations of mosquito nets may contribute to LLIN lower use by children over 5 years of age including the association between married status and LLIN use, which leads to the refusal of unmarried young men to sleep under LLINs; the custom of covering the dead with a mosquito net, which leads to fear of LLIN use; and taboos governing sleeping spaces for siblings of opposite sexes, which leads to LLIN shortages in households. Children under 5 years of age are known to be the most vulnerable age group for acquiring malaria and, therefore, are prioritized for LLIN use when there are limited supplies in households. In contrast, children over 5 years of age, who are perceived to be at less risk for malaria, often sleep without LLINs.ConclusionsPerceptions, social practices and regional beliefs regarding LLINs and vulnerability to malaria contribute to the nonuse of LLINs among children over 5 years of age in Madagascar. Modifying LLIN policies to account for these factors may increase LLIN use in this age group and reduce disease burden.

Background: Although it is accepted that long lasting insecticidal net (LLIN) use is an effective means to prevent malaria, children aged 5 to 15 years do not appear to be sufficiently protected in Madagascar; the malaria prevalence is highest in this age group. The purpose of this article is to summarize recent qualitative studies describing LLIN use among children aged 5-15 years and explore options to increase their use in this age group.Methods: Qualitative data from three studies on malaria conducted between 2012 and 2016 in 10 districts of Madagascar were analyzed. These studies cover all malaria epidemiological profiles and 10 of the 18 existing ethnic groups in Madagascar. A thematic analysis was conducted on the collected data from semi-structured interviews, direct observation data, and informal interviews.Results: A total of 192 semi-structured interviews were conducted. LLINs are generally perceived positively because they protect the health and well-being of users. However, regional representations of mosquito nets may contribute to LLIN nonuse by children over 5 years of age including the association between married status and LLIN use, which leads to the refusal of unmarried young men to sleep under LLINs; the custom of covering the dead with a mosquito net, which leads to fear of LLIN use; and taboos governing sleeping spaces for siblings of opposite sexes, which leads to LLIN shortages in households. Children under 5 years of age are known to be the most vulnerable age group for acquiring malaria and therefore are prioritized for LLIN use when there are limited supplies in households. In contrast, children over 5 years of age, who are perceived to be at less risk for malaria, often sleep without LLINs.Conclusions: Perceptions, social practices and regional beliefs regarding LLINs and vulnerability to malaria contribute to the nonuse of LLINs among children over 5 years of age in Madagascar. Modifying LLIN policies to account for these factors may increase LLIN use in this age group and reduce disease burden.Trial registration: Not applicable

Introduction: Manual (visually read) blood culture bottles (BCB) are frequently used in low-resource settings (LRS) where automated alternatives are less suitable. Yet performance evaluations of these BCBs are lacking, especially in comparison to automated systems. We evaluated two manual BCB types (the Bi-State BCB, Autobio; visually read BacT/ALERT bottles, bioMerieux) and used BacT/ALERT BCB monitored in a BacT/ALERT automate as a reference method. Methods: BCBs were spiked in triplicate with 177 clinical isolates representing pathogens frequently found in LRS (19 bacterial, 1 yeast species) for both adult and pediatric formulations. Growth in manual BCBs was evaluated by visually inspecting the broth, agar slant, and – for BacT/ALERT BCB – color change of the growth indicator. Blind subculture was conducted after overnight incubation (Day 1). Results: Overall yield was 95·9% and 95·5% for Bi-State and manual BacT/ALERT respectively, versus 96·1% for the reference method. The lowest yield occurred for Neisseria meningitidis and Burkholderia cepacia (83·3% and 83·1%) and was consistent among the three BC systems. On Day 1, growth was detected in 90·7% and 75·0% of grown BCBs in Bi-State and BacT/ALERT respectively, versus 99·3% for the reference method. On Day 2 detection rates were 100%, 97·7% and 100% respectively. Among 1013 grown Bi-State BCBs, growth mostly co-occurred in broth and slant (81·7%). Sufficient colony growth on the slant to perform further tests was present in only 44·1% and 59·0% of biphasic bottles on Day 2 and Day 3 respectively. Blind subculture generated colonies on Day 2 for 99·7% grown Bi-State and 99·2% of manual BacT/ALERT bottles respectively. Conclusion: In these in-vitro experiments, the yield and time-to-detection of manual BCBs were comparable to an automated system. Bi-State BCBs outperformed manual BacT/ALERT bottles, but the agar slant did not allow earlier detection nor earlier colony growth when compared to blind subculture on Day 1. Funding Statement: This research was funded by Medecins Sans Frontieres (Mini-Lab project). Medecins Sans Frontieres participated in study design, interpretation and writing of the manuscript. Declaration of Interests: None to declare. Ethics Approval Statement: Leftover blood from blood bank volunteers was used under research contract (file number CM20180327A). Clinical strains were obtained from ITM travel clinic and microbiological surveillance studies (Surveillance of antimicrobial resistance among consecutive blood culture isolates in tropical settings, Institutional Review Board 613/08, Ethical Committee University Hospital of Antwerp 8/20/96).

Malaria control programs implementing Long-Lasting Insecticidal Nets (LLINs) are encouraged to conduct field monitoring of nets’ survival, fabric integrity and insecticidal bio-efficacy. The reference method for testing the insecticide activity of LLINs needs 100 two-to-five-day-old female mosquitoes per net, which is highly resource-intensive. We aimed at identifying an alternative protocol, using fewer mosquitos, while ensuring a precision in the main indicator of ±5 percentage points (pp). We compared different laboratory methods against the probability of the LLIN to fail the test as determined by a hierarchical Bayesian model. When using 50 mosquitoes per LLIN and considering mortality only instead of mortality or knock-down as validity criteria, the average error in the measure of the proportion of nets considered as valid was 0.40 pp. The 95% confidence interval of this value never exceed 5 pp when the number of LLIN tested was ≥40. This method slightly outperforms the current recommendations. As a conclusion, testing the bio-efficacy of LLINs with half as many mosquitoes provides a valid evaluation of the proportion of valid LLINs. This approach could increase entomology labs’ testing capacity and decrease costs, with no impact in the decision process for public health purposes.

BackgroundAlthough it is accepted that long lasting insecticide bed net (LLIN) use is an effective means to prevent malaria, children aged 5 to 15 years do not appear to be sufficiently protected in Madagascar; malaria prevalence is highest in this age group. The purpose of this article is to summarize recent qualitative studies describing LLIN use among children aged 5–15 years and explore options to increase their use in this age group.MethodsQualitative data from three anthropological studies on malaria conducted between 2012 and 2016 in 10 districts of Madagascar were analyzed. These studies cover all malaria epidemiological profiles and 10 of the 18 existing ethnic groups in Madagascar. A thematic analysis was conducted on the collected data from semi-structured interviews, direct observation data, and informal interviews.ResultsA total of 192 semi-structured interviews were conducted. LLINs are generally perceived positively because they protect the health and well-being of users. However, regional representations of mosquito nets may contribute to LLIN nonuse by children over 5 years of age including the association between married status and LLIN use, which leads to the refusal of unmarried young men to sleep under LLINs; the custom of covering the dead with a mosquito net, which leads to fear of LLIN use; and taboos governing sleeping spaces for siblings of opposite sexes, which leads to LLIN shortages in households. Children under 5 years of age are known to be the most vulnerable age group for acquiring malaria and therefore are prioritized for LLIN use when there are limited supplies in households. In contrast, children over 5 years of age, who are perceived to be at less risk for malaria, often sleep without LLINs.ConclusionsPerceptions, social practices and regional beliefs regarding LLINs s and vulnerability to malaria contribute to the nonuse of LLINs among children over 5 years of age in Madagascar. Modifying LLIN policies to account for these factors may increase LLIN use in this age group and reduce disease burden.Trial registrationNot applicable

Background In low-malaria–transmission areas of Madagascar, annual parasite incidence (API) from routine data has been used to target indoor residual spraying at subdistrict commune level. To assess validity of this approach, we conducted school-based serological surveys and health facility (HF) data quality assessments in 7 districts to compare API to gold-standard commune-level serological measures. Methods At 2 primary schools in each of 93 communes, 60 students were randomly selected with parents and teachers. Capillary blood was drawn for rapid diagnostic tests (RDTs) and serology. Multiplex bead-based immunoassays to detect antibodies to 5 Plasmodium falciparum antigens were conducted, and finite mixture models used to characterize seronegative and seropositive populations. Reversible catalytic models generated commune-level annual seroconversion rates (SCRs). HF register data were abstracted to assess completeness and accuracy. Results RDT positivity from 12 770 samples was 0.5%. Seroprevalence to tested antigens ranged from 17.9% (MSP-1) to 59.7% (PF13). Median commune-level SCR was 0.0108 (range, 0.001–0.075). Compared to SCRs, API identified 71% (95% confidence interval, 51%–87%) of the 30% highest-transmission communes; sensitivity declined at lower levels. Routine data accuracy did not substantially affect API performance. Conclusions API performs reasonably well at identifying higher-transmission communes but sensitivity declined at lower transmission levels.

Background: The reduction of global malaria burden over the past 15 years is much attributed to the expansion of mass distribution campaigns (MDCs) of long-lasting insecticidal nets (LLIN). In Madagascar, two LLIN MDCs were implemented and one district also benefited from a community-based continuous distribution (CB-CD). Malaria incidence dropped but eventually rebounded after a decade. Methods: Data from a sentinel surveillance network over the 2009–2015 period was analyzed. Alerts were defined as weekly number of malaria cases exceeding the 90th percentile value for three consecutive weeks. Statistical analyses assessed the temporal relationship between LLIN MDCs and (i) number of malaria cases and (ii) malaria alerts detected, and (iii) the effect of a combination of MDCs and a CB-CD in Toamasina District. Findings: Analyses showed an increase of 13.6 points and 21.4 points in the percentile value of weekly malaria cases during the second and the third year following the MDC of LLINs respectively. The percentage of alert-free sentinel sites was 98.2% during the first year after LLIN MDC, 56.7% during the second year and 31.5% during the third year. The number of weekly malaria cases decreased by 14% during the CB-CD in Toamasina District. In contrast, sites without continuous distribution had a 12% increase of malaria cases. Interpretation: These findings support the malaria-preventive effectiveness of MDCs in Madagascar but highlight their limited duration when not followed by continuous distribution. The resulting policy implications are crucial to sustain reductions in malaria burden in high transmission settings. Keywords: Malaria, Madagascar, LLINs effectiveness, Sentinel surveillance

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections.

ObjectivesTo investigate the feasibility of establishing hospital-based antimicrobial stewardship (AMS) programmes comprising action-planning, educational interventions and data feedback in two provincial-level hospitals in Viet Nam.Design and settingThis was an implementation research using participatory action process and existing resources from the Duke Antimicrobial Stewardship Outreach Network with local adjustments. A national stakeholder meeting and Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis were conducted to identify gaps and potential interventions.ParticipantsHospital AMS staff implemented activities throughout the study phases. Routinely collected patient data were analysed to support planning, implementation and evaluation.InterventionsHospitals were considered as a complex adaptive system and leveraged their unique characteristics and interconnections to develop 1-year plans containing core interventions (data use, educational training, prospective audit with feedback (PAF) and evaluations).Outcome measuresWe assessed feasibility using outputs from stakeholder meeting, SWOT analysis, baseline data, planning process and implementation.ResultsThe stakeholder meeting identified three gaps for AMS at national level: supportive policies, AMS training and core competencies and collaboration. At the hospitals, AMS programmes took 1 year for planning due to lack of hospital-specific procedures and relevant staff competencies. Baseline data (January–December 2019) showed variations in antibiotic consumption: 951 days of therapy (DOT) per 1000 days present in the control and 496 in the intervention wards in hospital 1, and 737 and 714 in hospital 2, respectively. During 1-year implementation, clinical pharmacists audited 1890 antibiotic prescriptions in hospital 1 (June 2020–May 2021) and 1628 in hospital 2 (July 2020–July 2021), and will continue PAF in their daily work.ConclusionOur data confirmed the need to contextualise AMS programmes in low-income and middle-income countries (LMICs) and demonstrated the usefulness of implementation research design in assessing programme feasibility. Developing staff competencies, using local data to stimulate actions and integrating programme activities in routine hospital work are key to success in LMICs.

Background Because international funding for malaria control is plateauing, affected countries that receive foreign funding are expected to maintain a constant budget while continuing to reduce Plasmodium transmission. To investigate the appropriateness of a malaria control policy in Madagascar, the effectiveness of all currently deployed malaria control interventions (MCIs) was measured. Methods A nationwide cross-sectional survey was conducted in 2012–2013 at 62 sites throughout Madagascar. A total of 15,746 individuals of all ages were tested for Plasmodium infection using rapid diagnostic tests and were interviewed about their use of long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), intermittent preventive treatment of pregnant women (IPTp), and exposure to information, education and communication (IEC) campaigns. The association between Plasmodium infection and MCI exposure was calculated using multivariate multilevel models, and the protective effectiveness (PE) of an intervention was defined as one minus the odds ratio of this association. Results The individual PE of regular LLIN use was high and significant (41 %, 95 % confidence interval [CI] 23–54), whereas its community PE was not. The PE of IRS at the household level was significant in one transmission pattern only (44 %, 95 % CI 11–65), and the community PE with high IRS coverage (>75 %) was high and significant overall (78 %, 95 % CI 44–91). Using LLINs after IRS increased the PE, and the reciprocal was also true. The maternal PE of IPTp was high but non-significant (65 %, 95 % CI −32 to 91). The PE of IEC was low, non-significant and restricted to certain areas (24 %, 95 % CI −34 to 57). Conclusions This snapshot of the effectiveness of MCIs confirms that integrated vector control is required in malaria control policies in Madagascar and suggests combining MCIs when one is questionable. Policymakers should consider the local effectiveness of all deployed MCIs through a similar phase IV assessment. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1376-5) contains supplementary material, which is available to authorized users.

Background Although its incidence has been decreasing during the last decade, malaria is still a major public health issue in Madagascar. The use of Long Lasting Insecticidal Nets (LLIN) remains a key malaria control intervention strategy in Madagascar, however, it encounters some obstacles. The present study aimed to explore the local terminology related to malaria, information channels about malaria, attitude towards bed nets, and health care seeking practices in case of fever. This article presents novel qualitative findings about malaria. Until now, no such data has been published for Madagascar. Methods A comparative qualitative study was carried out at four sites in Madagascar, each differing by malaria epidemiology and socio-cultural background of the populations. Seventy-one semi-structured interviews were conducted with biomedical and traditional caregivers, and members of the local population. In addition, observations of the living conditions and the uses of bed net were conducted. Results Due to the differences between local and biomedical perspectives on malaria, official messages did not have the expected impact on population in terms of prevention and care seeking behaviors. Rather, most information retained about malaria was spread through informal information circulation channels. Most interviewees perceived malaria as a disease that is simple to treat. Tazomoka (“mosquito fever”), the Malagasy biomedical word for malaria, was not used by populations. Tazo (“fever”) and tazomahery (“strong fever”) were the terms more commonly used by members of the local population to refer to malaria related symptoms. According to local perceptions in all areas, tazo and tazomahery were not caused by mosquitos. Each of these symptoms required specific health recourse. The usual fever management strategies consisted of self-medication or recourse to traditional and biomedical caregivers. Usage of bed nets was intermittent and was not directly linked to protection against malaria in the eyes of most Malagasy people. Conclusions This article highlights the conflicting understanding of malaria between local perceptions and the biomedical establishment in Madagascar. Local perceptions of malaria present a holistic vision of the disease that includes various social and cultural dimensions, rather than reflecting one universal understanding, as in the biomedical image. The consideration of this “holistic vision” and other socio-cultural aspects surrounding the understanding of malaria is essential in implementing successful control intervention strategies.

Background Madagascar, as other malaria endemic countries, depends mainly on international funding for the implementation of malaria control interventions (MCI). As these funds no longer increase, policy makers need to know whether these MCI actually provide the expected protection. This study aimed at measuring the effectiveness of MCI deployed in all transmission patterns of Madagascar in 2012–2013 against the occurrence of clinical malaria cases. Methods From September 2012 to August 2013, patients consulting for non-complicated malaria in 31 sentinel health centres (SHC) were asked to answer a short questionnaire about long-lasting insecticidal nets (LLIN) use, indoor residual spraying (IRS) in the household and intermittent preventive treatment of pregnant women (IPTp) intake. Controls were healthy all-ages individuals sampled from a concurrent cross-sectional survey conducted in areas surrounding the SHC. Cases and controls were retained in the database if they were resident of the same communes. The association between Plasmodium infection and exposure to MCI was calculated by multivariate multilevel models, and the protective effectiveness (PE) of an intervention was defined as 1 minus the odds ratio of this association. Results Data about 841 cases (out of 6760 cases observed in SHC) and 8284 controls was collected. The regular use of LLIN provided a significant 51 % PE (95 % CI [16–71]) in multivariate analysis, excluding in one transmission pattern where PE was −11 % (95 % CI [−251 to 65]) in univariate analysis. The PE of IRS was 51 % (95 % CI [31–65]), and the PE of exposure to both regular use of LLIN and IRS was 72 % (95 % CI [28–89]) in multivariate analyses. Vector control interventions avoided yearly over 100,000 clinical cases of malaria in Madagascar. The maternal PE of IPTp was 73 %. Conclusions In Madagascar, LLIN and IRS had good PE against clinical malaria. These results may apply to other countries with similar transmission profiles, but such case–control surveys could be recommended to identify local failures in the effectiveness of MCI. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1132-x) contains supplementary material, which is available to authorized users.

Borrelia burgdorferi sensu lato is a genetically diverse group of spirochetes that includes the agent of Lyme borreliosis in which genospecies tend to be associated with specific clinical features. The aim of the study was to determine the prevalence and genetic diversity of Borrelia burgdorferi sensu lato in 524 ticks collected in woods of a western province of Belgium. Presence of spirochetes in ticks was determined by phase contrast microscopy. The mean infection rate of ticks was 12.0%. Variability was observed in the prevalence of infection among the five sites examined, ranging from 2.8 to 21.6%. Identification to genospecies was determined by PCR and sequencing. The most common genomospecies were Borrelia afzelii (55%) and Borrelia garinii (21%). For the first time in Belgium, we detected Borrelia valaisiana and Borrelia spielmanii, representing 14% and 2%, respectively. Borrelia burgdorferisensu stricto counted only for 2%. Co-infections were present in 8% of ticks. We emphasize the need for clinical studies to assess the prevalence of specific genospecies-related clinical manifestations of Lyme borreliosis in Belgium.

Background: Community-acquired pneumonia (CAP), a leading cause of mortality, mainly affects children in developing countries. The harsh circumstances experienced by refugees include various factors associated with respiratory pathogen transmission, and clinical progression of CAP. Consequently, the etiology of CAP in humanitarian crisis situations may differ to that of settled populations, which would impact appropriate case management. Therefore, the Pneumonia Etiology Among Refugees and the Lebanese population (PEARL) study was initiated with the objective of identifying the causal pathogenic microorganisms in the respiratory tract of children and adults from both the refugee and host country population presenting with signs of CAP during a humanitarian crisis. Methods: PEARL, a prospective, multicentric, case-control study, will be conducted at four primary healthcare facilities in Tripoli and the Bekaa valley over 15 months (including two high-transmission seasons/winters). Sociodemographic and medical data, and biological samples will be collected from at least 600 CAP cases and 600 controls. Nasopharyngeal swabs, sputum, urine and blood samples will be analyzed at five clinical pathology laboratories in Lebanon to identify the bacterial and viral etiological agents of CAP. Transcriptomic profiling of host leukocytes will be performed. Conclusions: PEARL is an original observational study that will provide important new information on the etiology of pneumonia among refugees, which may improve case management, help design antimicrobial stewardship interventions, and reduce morbidity and mortality due to CAP in a humanitarian crisis.

Background The impact of migration and country or region of origin on sexual behaviours and prevention of the sexual transmission of HIV has been scarcely studied in France. The objective of this study was to evaluate if and how individual attitudes of prevention towards HIV infection are different according to country or region of origins in Paris area, France. Methods 3006 individuals were interviewed in the Paris metropolitan area in 2010. Outcome variables were (i) the intention of the individual to protect oneself against HIV, and (ii) the adoption of a condom-based approach for protection against HIV. To explore factors associated with these outcomes, we constructed multivariate logistic regression models, first taking into account only demographic variables –including country of origin-, then successively adding socioeconomic variables and variables related to sexual behaviour and HIV perception and prevention behaviour. Results French and foreign people who have origins in Sub-Saharan Africa declared more intentions to protect themselves than French people with French parents (in foreign men, aOR = 3.43 [1.66–7.13]; in foreign women, aOR = 2.94 [1.65–5.23]), but did not declare more recourse to a condom-based approach for protection against HIV (in foreign men, aOR = 1.38 [0.38–4.93]; in foreign women, aOR = 0.93 [0.40–2.18]). Conversely, foreign women and French women from foreign origin, especially from Maghreb (Northern Africa), reported less intention of protection than French women with French parents. Conclusions These results underline the importance of taking culture and origins of target populations into consideration when designing information, education and communication about HIV and sexually transmitted diseases. These results also draw attention to fractions of the general population that could escape from prevention messages. Electronic supplementary material The online version of this article (doi:10.1186/s12889-015-2051-4) contains supplementary material, which is available to authorized users.

Background In the last decade, an important scale-up was observed in malaria control interventions. Madagascar entered the process for pre-elimination in 2007. Policy making needs operational indicators, but also indicators about effectiveness and impact of malaria control interventions (MCI). This study is aimed at providing data about malaria infection, morbidity, and mortality, and MCI in Madagascar. Methods Two nationwide surveys were simultaneously conducted in 2012–2013 in Madagascar: a study about non-complicated clinical malaria cases in 31 sentinel health facilities, and a cross-sectional survey (CSS) in 62 sites. The CSS encompassed interviews, collection of biological samples and verbal autopsies (VA). Data from CSS were weighted for age, sex, malaria transmission pattern, and population density. VA data were processed with InterVA-4 software. Results CSS included 15,746 individuals of all ages. Parasite rate (PR) as measured by rapid diagnostic tests was 3.1%, and was significantly higher in five to 19 year olds, in males, poorer socio-economic status (SES) quintiles and rural areas. Long-lasting insecticidal nets (LLIN) use was 41.7% and was significantly lower in five to 19 year olds, males and wealthier SES quintiles. Proportion of persons covered by indoor residual spraying (IRS) was 66.8% in targeted zones. Proportion of persons using other insecticides than IRS was 22.8%. Coverage of intermittent preventive treatment during pregnancy was 21.5%. Exposure to information, education and communication messages about malaria was significantly higher in wealthier SES for all media but information meetings. The proportion of fever case managements considered as appropriate with regard to malaria was 15.8%. Malaria was attributed as the cause of death in 14.0% of 86 VA, and 50% of these deaths involved persons above the age of five years. The clinical case study included 818 cases of which people above the age of five accounted for 79.7%. In targeted zones, coverage of LLIN and IRS were lower in clinical cases than in general population. Conclusions This study provides valuable data for the evaluation of effectiveness and factors affecting MCI. MCI and evaluation surveys should consider the whole population and not only focus on under-fives and pregnant women in pre-elimination or elimination strategies. Electronic supplementary material The online version of this article (doi:10.1186/1475-2875-13-465) contains supplementary material, which is available to authorized users.

Infliximab is a human-murine chimeric monoclonal antibody directed against tumor necrosis factor alpha (TNFalpha). Infliximab and other TNF blockers are used to treat inflammatory diseases such as rheumatoid arthritis (RA). TNF blockers are suspected to play a key role in some infections. We report here two cases of Listeria monocytogenes sepsis associated with infliximab treatment for RA. The first patient developed a terminal ileitis and a bacteraemia after three doses of infliximab; the second RA patient presented a bacteraemia associated with a prosthetic joint arthritis of the left hip, both related to Listeria. Those two cases occurred in a population of 518 patients treated with TNF blockers in our hospitals since the year 2000. Those events are of particular interest because of the severity of the infection, because the treatment differs from other infections, and because that, in the rheumatology unit, septic arthritis can mimic RA symptoms. They enhance the likelihood for this drug to increase the risk for infections with germs like Listeria.

WOS: 000323285500054, PubMed ID: 23836184, Extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBL E. coli) strains are of major concern because few antibiotics remain active against these bacteria. We investigated the association between the fecal relative abundance (RA) of ESBL-producing E. coli (ESBL-RA) and the occurrence of ESBL E. coli urinary tract infections (UTIs). The first stool samples passed after suspicion of UTI from 310 women with subsequently confirmed E. coli UTIs were sampled and tested for ESBL-RA by culture on selective agar. Predictive values of ESBL-RA for ESBL E. coli UTI were analyzed for women who were not exposed to antibiotics when the stool was passed. ESBL E. coli isolates were characterized for ESBL type, phylogroup, relatedness, and virulence factors. The prevalence of ESBL E. coli fecal carriage was 20.3%, with ESBL E. coli UTIs being present in 12.3% of the women. The mean ESBL-RA (95% confidence interval [CI]) was 13-fold higher in women exposed to antibiotics at the time of sampling than in those not exposed (14.3% [range, 5.6% to 36.9%] versus 1.1% [range, 0.32% to 3.6%], respectively; P, ECO-NET (an Egide program); FP7 Health Program (EvoTAR project) [282004]; FP7 Health Program (R-GNOSIS project) [282512]; Oseo (Nosobio program); Federation of European Microbiological Societies (FEMS Research Fellowship), This work was supported in part by ECO-NET (an Egide program [http://www.egide.asso.fr/]), by the FP7 Health Program (EvoTAR project, contract no. 282004, and R-GNOSIS project, contract no. 282512), and by Oseo (http://www.oseo.fr/) (Nosobio program). T. K. was supported by a grant from the Federation of European Microbiological Societies (FEMS Research Fellowship).

Background The malaria burden in Madagascar dropped down last decade, largely due to scale-up of control measures. Nevertheless, a significant rise of malaria cases occurred in 2011–2012 in two regions of the rainy South-Eastern Madagascar, where malaria is considered as mesoendemic and the population is supposed to be protected by its acquired immunity against Plasmodium. A multidisciplinary investigation was conducted in order to identify the causes of the outbreak. Methods In March 2012, a cross-sectional study was conducted in 20 randomly selected clusters, involving the rapid diagnostic testing of all ≥6 month-old members of households and a questionnaire about socio-demographic data and exposure to malaria control interventions. Changes in environmental conditions were evaluated by qualitative interview of local authorities, climatic conditions were evaluated by remote-sensing, and stock outs of malaria supplies in health facilities were evaluated by quantitative means. Two long-lasting insecticidal nets (LLINs) were sampled in each cluster in order to evaluate their condition and the remanence of their insecticidal activity. The entomological investigation also encompassed the collection Anopheles vectors in two sites, and the measure of their sensitivity to deltamethrin. Results The cross-sectional survey included 1615 members of 440 households. The mean Plasmodium infection rate was 25.6 % and the mean bed net use on the day before survey was 71.1 %. The prevalence of Plasmodium infections was higher in 6–14 year-old children (odds ratio (OR) 7.73 [95 % CI 3.58–16.68]), in rural areas (OR 6.25 [4.46–8.76]), in poorest socio-economic tercile (OR 1.54 [1.13–2.08]), and it was lower in individuals sleeping regularly under the bed net (OR 0.51 [0.32–0.82]). Stock outs of anti-malarial drugs in the last 6 months have been reported in two third of health facilities. Rainfalls were increased as compared with the three previous rainy seasons. Vectors collected were sensitive to pyrethroids. Two years after distribution, nearly all LLINs collected showed a loss of physical integrity and insecticide activity, Conclusions Increased rainfall, decreasing use and reduced insecticide activity of long-lasting insecticide-treated nets, and drug shortages may have been responsible for, or contributed to, the outbreak observed in South-Eastern Madagascar in 2011–2012. Control interventions for malaria elimination must be sustained at the risk of triggering harmful epidemics, even in zones of high transmission.

The impact of disease control can be either evaluated by a classical ecological study, or by multiplication of the effectiveness of control intervention and the disease burden. The latter approach has the advantage of circumventing ecological biases. To evaulate the effectiveness of the malaria control program implemented in Madagascar, we conducted a nationwide survey in 2012-2013 in 62 study sites. This survey included (1) a cross-sectional study to measure the effectiveness of each control intervention on reducing the transmission, and (2) a case-control study to measure the effectiveness on reducing the morbidity. We present here the results related to vector control interventions, i.e. Long Lasting Insecticidal Nets (LLIN) distribution and Indoor Residual Spraying (IRS) campaigns. The cross-sectional survey included 15,734 individuals of all age groups among which 3.7% had a positive Rapid Diagnostic Test (RDT). LLIN daily use was 52.3% in areas covered by universal distribution and IRS coverage was 64.8% in targeted areas. 818 uncomplicated clinical malaria cases were compared to 7,767 controls living in the same villages. Multilevel analysis of factors associated with a positive RDT or with the occurrence of an episode of non-complicated malaria revealed that LLIN daily use had a 45% protective effectiveness (PE) against infection (aOR 0.55 [95% CI 0.42, 0.72]) and a 48% PE against morbidity (aOR 0.52 [0.28, 0.96]). The PE of IRS was evaluated to be 23% against infection (aOR 0.77 [0.53, 1.13]) and 49% against morbidity (aOR 0.51 [0.39, 0.66]). In areas where both activities are implemented, coverage of LLIN was 21.3 percentage points lower than in areas where LLIN only were deployed. Combining IRS with LLIN provided almost no gain in preventing infection, but the PE of LLIN use against morbidity increased from 51% (aOR 0.49 [0.20, 1.20]) to 66% (aOR 0.34 [0.16, 0.74]) when IRS was added, although non significantly. Our results indicate that, taken separately, LLIN and IRS perform satisfactorily but that their concurrent use might have a limited benefit as compared with efforts to improve the coverage of a single intervention. Given that in Madagascar, approx. 220,000 clinical malaria cases and 770,000 malaria infections occur each year, we calculated that vector control interventions prevented approx. 96,000 malaria cases and 197,000 malaria infections annually. Distributions of LLIN were implicated in the major part of cases (73.7%) and infections (80.5%) prevented, while IRS campaigns were implicated in 37.3% of cases and 31.2% of infections prevented.