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Introduction The rise of antimicrobial resistance represents a critical threat to global health, exacerbated by the excessive and inappropriate dispensing and use of antimicrobial drugs, notably antibiotics, which specifically target bacterial infections. The surge in antibiotic consumption globally is particularly concerning in low-income and middle-income countries (LMICs), where informal healthcare providers (IPs) play a vital role in the healthcare landscape. Often the initial point of contact for healthcare-seeking individuals, IPs play a crucial role in delivering primary care services in these regions. Despite the prevalent dispensing of antibiotics by IPs in many LMICs, as highlighted by existing research, there remains a gap in the comprehensive synthesis of antibiotic dispensing practices and the influencing factors among IPs. Hence, this scoping review seeks to map and consolidate the literature regarding antibiotic dispensing and its drivers among IPs in LMICs.Methods and analysis This review will follow the Joanna Briggs Institute guideline for scoping review. A comprehensive search across nine electronic databases (MEDLINE, EMBASE, SCOPUS, Global Health, CINAHL, Web of Science, LILACS, AJOL and IMSEAR) will be performed, supplemented by manual searches of reference lists of eligible publications. The search strategy will impose no constraints on study design, methodology, publication date or language. The study selection process will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The findings on antibiotic dispensing and its patterns will be synthesised and reported descriptively using tables, visuals and a narrative summary. Additionally, factors influencing antibiotic dispensing will be elucidated through both inductive and deductive content analysis methods.Ethics and dissemination Ethical approval is not required for scoping reviews. The findings will be disseminated through peer-reviewed publications and presentations at relevant conferences.

Abstract Background Sex and gender are believed to influence vaccine response. Yet, the relationship between sex and gender and COVID-19 vaccine efficacy is poorly understood and remains under-investigated. Methods We conducted a systematic review to determine whether and to what extent post-approval COVID-19 vaccine effectiveness (VE) studies report sex-disaggregated VE data. We searched four publication and pre-publication databases and additional grey literature sources for relevant published/preprint studies released between 1 January 2020 and 1 October 2021 (i.e., pre-Omicron era). We included observational studies providing VE estimates for one or more licensed/approved COVID-19 vaccines and including both males and females. Two reviewers independently assessed study eligibility, extracted data, and assessed risk-of-bias through a modified version of Cochrane’s ROBINS-I tool. A qualitative data synthesis was performed. Results Here we show that, among 240 eligible publications, 68 (28.3%) do not report the sex distribution among participants. Only 21/240 (8.8%) studies provide sex-disaggregated VE estimates, and high between-study heterogeneity regarding design, target population, outcomes, and vaccine type/timing prevent the assessment of sex in determining COVID-19 VE across studies. Conclusions Our findings indicate that few COVID-19 vaccine research publications account for sex. Improved adherence to recommended reporting guidelines will ensure that the evidence generated can be used to better understand the relationship between sex and gender and VE.

As the first point of care for many healthcare seekers, private pharmacies play an important role in tuberculosis (TB) care. However, previous studies in India have showed that private pharmacies commonly dispense symptomatic treatments and broad-spectrum antibiotics over-the-counter (OTC), rather than referring patients for TB testing. Such inappropriate management by pharmacies can delaye TB diagnosis. We assessed medical advice and OTC drug dispensing practices of pharmacists for standardized patients presenting with classic symptoms of pulmonary TB (case 1) and for those with sputum smear positive pulmonary TB (case 2), and examined how practices have changed over time in an urban Indian site. We examined how and whether private pharmacies improved practices for TB in 2019 compared to a baseline study conducted in 2015 in the city of Patna, using the same survey sampling techniques and study staff. The proportion of patient-pharmacist interactions that resulted in correct or ideal management, as well as the proportion of interactions resulting in antibiotic, quinolone, and corticosteroid are presented, with standard errors clustered at the provider level. To assess the difference in case management and the use of drugs across the two cases by round, a difference in difference (DiD) model was employed. A total of 936 SP interactions were completed over both rounds of survey. Our results indicate that across both rounds of data collection, 331 of 936 (35%; 95% CI: 32-38%) of interactions were correctly managed. At baseline, 215 of 500 (43%; 95% CI: 39-47%) of interactions were correctly managed whereas 116 of 436 (27%; 95% CI: 23-31%) were correctly managed in the second round of data collection. Ideal management, where in addition to a referral, patients were not prescribed any potentially harmful medications, was seen in 275 of 936 (29%; 95% CI: 27-32%) of interactions overall, with 194 of 500 (39%; 95% CI: 35-43%) of interactions at baseline and 81 of 436 (19%; 95% CI: 15-22%) in round 2. No private pharmacy dispensed anti-TB medications without a prescription. On average, the difference in correct case management between case 1 vs. case 2 dropped by 20 percent points from baseline to the second round of data collection. Similarly, ideal case management decreased by 26 percentage points between rounds. This is in contrast with the dispensation of medicines, which had the opposite effect between rounds; the difference in dispensation of quinolones between case 1 and case 2 increased by 14 percentage points, as did corticosteroids by 9 percentage points, antibiotics by 25 percentage points and medicines generally by 30 percentage points. Our standardised patient study provides valuable insights into how private pharmacies in an Indian city changed their management of patients with TB symptoms or with confirmed TB over a 5-year period. We saw that overall, private pharmacy performance has weakened over time. However, no OTC dispensation of anti-TB medications occurred in either survey round. As the first point of contact for many care seekers, continued and sustained efforts to engage with Indian private pharmacies should be prioritized.

Background and objectives India, the country with the largest market availability of antimicrobial fixed-dose combinations (FDCs), banned certain antimicrobial FDCs in September 2018. Our objective was to examine the impact of Government ban on the sales of antimicrobial FDCs. Methods The sales patterns of 14 of the 26 banned antimicrobial FDCs were analyzed using monthly private sector drug sales data from IQVIA (a comprehensive and nationally representative drug sales database) between January 2018 and December 2019. We carried out descriptive analyses to evaluate the trend in sales over time for banned and non-banned antimicrobial FDCs using cumulative sales volumes. Results Overall, the cumulative sales volume of banned antimicrobial FDCs declined by 75% between January and September 2018 and the same months of 2019, although some banned FDCs continued to be available in significant volumes. The effectiveness of the ban was offset by several pathways. First, the sales of combinations containing moieties belonging to the same drug-classes as the antimicrobials in the banned FDCs increased after the ban. Second, while certain formulations of particular combinations were banned, the sales of other non-banned formulation of these combinations increased. Third, in some cases, products containing new non-antimicrobial components added to the banned combinations remained available. Interpretation and conclusions While sales of the banned antimicrobial FDCs decreased in 2019, we identified several mechanisms that counterbalanced the ban, including implementation failure, rising sales of congeners, and products with additional non-antimicrobial components.

Introduction Low and varied quality of care has been demonstrated for childhood illnesses in low-income and middle-income countries. Some quality improvement strategies focus on increasing patient engagement; however, evidence suggests that patients demanding medicines can favour the selection of resistant microbial strains in the individual and the community if drugs are inappropriately used. This study examines the effects on quality of care when patients demand different types of inappropriate medicines.Methods We conducted an experiment where unannounced standardised patients (SPs), locally recruited individuals trained to simulate a standardised case, present at private clinics. Between 8 March and 28 May 2019, 10 SPs portraying caretakers of a watery diarrhoea childhood case scenario (in absentia) conducted N=200 visits at 200 private, primary care clinics in Kenya. Half of the clinics were randomly assigned to receive an SP demanding amoxicillin (an antibiotic); the other half, an SP demanding albendazole (an antiparasitic drug often used for deworming), with other presenting characteristics the same. We used logistic and linear regression models to assess the effects of demanding these inappropriate medicines on correct and unnecessary case management outcomes.Results Compared with 3% among those who did not demand albendazole, the dispensing rate increased significantly to 34% for those who did (adjusted OR 0.06, 95% CI 0.02 to 0.22, p

Abstract Background This study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection. Methods This is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay. Results The Cmax and AUC0–12h medians in arm A (Cmax = 296 ng/mL, IQR: 205–45; AUC0–12h = 2528 ng.h/mL, IQR: 1684–2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403–717; AUC0–12h = 4042.5 ng.h/mL, IQR: 3469–5761), with a statistically significant difference in AUC0–12h (p = 0.044) but not in Cmax (p = 0.313). No significant differences were observed in Tmax (3 h versus 4 h). Five patients had a Cmax below the plasma therapeutic limit ( 64 ng/mL) in the 300 mg RBT arm, while 4/9 patients had such values in the 150 mg RBT arm. Conclusion This study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria. Trial registration PACTR201310000629390 , 28th October 2013.

Abstract Background To evaluate the pharmacokinetic of plasma lopinavir (LPV) and ritonavir (RTV) when co-administered with three times weekly (TPW) rifabutin (RBT) at a dose of either 150 or 300 mg in African tuberculosis (TB) and HIV co-infected adult patients. Methods This is a pharmacokinetic study conducted in Ouagadougou among patients treated with a standard dosage of LPV/RTV 400/100 mg twice daily and RBT 150 mg TPW (arm A = 9 patients) or rifabutin 300 mg TPW (arm B = 7 patients) based regimens. Patients were recruited from the Bogodogo and Kossodo district hospitals in Ouagadougou from May 2013 to December 2015. Study inclusion criteria were that the patients were between 18 and 60 years of age, HIV-1 infected with pulmonary tuberculosis confirmed or suspected. Subsequent blood samples for pharmacokinetic monitoring were collected at 1, 2, 3, 4, 6, 8 and 12 h after combined drug ingestion for plasma drug monitoring using HPLC/MS assays. Results The medians LPV Cmax and Tmax were respectively, 20 μg/mL and 4 h for the RBT 150 mg group (arm A) and 7.7 μg/mL and 3 h for the RBT 300 mg group (arm B). The AUC0–12 of LPV was 111.8 μg h/mL in patients belonging to arm A versus 69.9 μg/mL for those in arm B (p = 0.313). The C0 of LPV was lower than 4 μg/mL in three patients receiving RBT 300 mg. Of note, the RTV plasma concentrations were nearly halved among patients on RBT 300 mg compared to those on lower RBT doses. The AUC0–12 of RTV in arm A was 12.7 μg h/mL versus 6.6 μg h/ml in arm B (p = 0.313). Conclusion In our study, the pharmacokinetic of LPV and RTV was found to be highly variable when coadministrated with RBT 150 mg or 300 mg three times per week. There is a need for specific large study to verify clinical and virological effects of this variation, especially when coadministrated with RBT of 300 mg TPW, and to prevent viral resistance in response to under-dosing of LPV. Trial registration PACTR201310000629390. Registered 28 October 2013, http://www.pactr.org/

Introduction In Canada, pneumococcal vaccination is recommended to all adults aged ≥65 and those Methods Using data from a large national cohort of Canadian residents aged ≥47 years between 2015–2018, we calculated self-reported pneumococcal vaccine uptake among eligible groups, estimated associations between key factors and non-vaccination, assessed missed opportunities for vaccination (MOV) and examined risk factors for MOV. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for relevant associations were estimated through logistic regression. Results 45.8% (95% CI: 45.2–46.5) of 22,246 participants aged ≥65 and 81.3% (95% CI: 80.5–82.0) of 10,815 individuals aged 47–64 with ≥1 CMC reported never having received a pneumococcal vaccine. Receipt of influenza vaccination in the previous year was associated with the lowest odds of pneumococcal non-vaccination (aOR = 0.14 [95% CI: 0.13–0.15] for older adults and aOR = 0.23 [95% CI: 0.20–0.26] for those aged 47–64 with ≥1 CMC). Pneumococcal vaccine uptake was also more likely in case of contact with a family doctor in the previous year (versus no contact), increased with age and varied widely across provinces. Among individuals recently vaccinated against influenza, 32.6% (95% CI: 31.9–33.4) of those aged ≥65 and 71.1% (95% CI: 69.9–72.3) of those aged 47–64 with ≥1 CMC missed an opportunity to get a pneumococcal vaccine. Among individuals who had contact with a family doctor, 44.8% (95% CI: 44.1–45.5) of those aged ≥65 and 80.4% (95% CI: 79.6–81.2) of those aged 47–64 with ≥1 CMC experienced a MOV. Conclusions Pneumococcal vaccine uptake remains suboptimal among at-risk Canadian adults who are eligible for vaccination. Further research is needed to clarify the reasons behind missed opportunities for vaccination and adequately address the main barriers to pneumococcal vaccination.

IntroductionIn Canada, pneumococcal vaccination is recommended to all adults aged ≥65 and those MethodsUsing data from a large national cohort of Canadian residents aged ≥47 years between 2015-2018, we calculated self-reported pneumococcal vaccine uptake among eligible groups, estimated associations between key factors and non-vaccination, assessed missed opportunities for vaccination (MOV) and examined risk factors for MOV. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for relevant associations were estimated through logistic regression.Results45.8% (95% CI: 45.2-46.5) of 22,246 participants aged ≥65 and 81.3% (95% CI: 80.5-82.0) of 10,815 individuals aged 47-64 with ≥1 CMC reported never having received a pneumococcal vaccine. Receipt of influenza vaccination in the previous year was associated with the lowest odds of pneumococcal non-vaccination (aOR = 0.14 [95% CI: 0.13-0.15] for older adults and aOR = 0.23 [95% CI: 0.20-0.26] for those aged 47-64 with ≥1 CMC). Pneumococcal vaccine uptake was also more likely in case of contact with a family doctor in the previous year (versus no contact), increased with age and varied widely across provinces. Among individuals recently vaccinated against influenza, 32.6% (95% CI: 31.9-33.4) of those aged ≥65 and 71.1% (95% CI: 69.9-72.3) of those aged 47-64 with ≥1 CMC missed an opportunity to get a pneumococcal vaccine. Among individuals who had contact with a family doctor, 44.8% (95% CI: 44.1-45.5) of those aged ≥65 and 80.4% (95% CI: 79.6-81.2) of those aged 47-64 with ≥1 CMC experienced a MOV.ConclusionsPneumococcal vaccine uptake remains suboptimal among at-risk Canadian adults who are eligible for vaccination. Further research is needed to clarify the reasons behind missed opportunities for vaccination and adequately address the main barriers to pneumococcal vaccination.

BackgroundInfluenza vaccination is recommended in Canada for older adults and those with underlying health conditions due to their increased risk of severe outcomes. Further research is needed to identify who within these groups is not receiving influenza vaccine to identify opportunities to increase coverage.ObjectivesWe aimed to 1) estimate influenza non-vaccination prevalence and 2) assess factors associated with non-vaccination among Canadian adults aged ≥65 and adults aged 46-64 with ≥1 chronic medical condition (CMC) due to their high risk of severe influenza outcomes.MethodsWe conducted a secondary analysis of cross-sectional data collected from 2015-2018 among participants of the Canadian Longitudinal Study on Aging. For both groups of interest, we estimated non-vaccination prevalence and used logistic regression models to identify factors associated with non-vaccination. We report adjusted odds ratios and 95% confidence intervals for the investigated variables.ResultsOverall, 29.5% (95% CI: 28.9%, 30.1%) of the 23,226 participants aged ≥65 years and 50.4% (95% CI: 49.4%, 51.3%) of the 11,250 participants aged 46-64 years with ≥1 CMC reported not receiving an influenza vaccination in the past 12 months. For both groups, lack of recent contact with a family doctor and current smoking were independently associated with non-vaccination.DiscussionInfluenza vaccination helps prevent severe influenza outcomes. Yet, half of adults aged 46-64 years with ≥1 CMC and more than one-quarter of all adults aged ≥65 years did not receive a recommended influenza vaccine in the year prior to the survey. Innovation in vaccination campaigns for routinely recommended vaccines, especially among those without annual family doctor visits, may improve coverage.ConclusionInfluenza vaccination coverage among Canadian adults aged 46-64 years with ≥1 CMC and adults aged ≥65 years remains suboptimal. Vaccination campaigns targeting those at high risk of severe outcomes without routine physician engagement should be evaluated to improve uptake.

Background Influenza vaccination is recommended in Canada for older adults and those with underlying health conditions due to their increased risk of severe outcomes. Further research is needed to identify who within these groups is not receiving influenza vaccine to identify opportunities to increase coverage. Objectives We aimed to 1) estimate influenza non-vaccination prevalence and 2) assess factors associated with non-vaccination among Canadian adults aged ≥65 and adults aged 46–64 with ≥1 chronic medical condition (CMC) due to their high risk of severe influenza outcomes. Methods We conducted a secondary analysis of cross-sectional data collected from 2015–2018 among participants of the Canadian Longitudinal Study on Aging. For both groups of interest, we estimated non-vaccination prevalence and used logistic regression models to identify factors associated with non-vaccination. We report adjusted odds ratios and 95% confidence intervals for the investigated variables. Results Overall, 29.5% (95% CI: 28.9%, 30.1%) of the 23,226 participants aged ≥65 years and 50.4% (95% CI: 49.4%, 51.3%) of the 11,250 participants aged 46–64 years with ≥1 CMC reported not receiving an influenza vaccination in the past 12 months. For both groups, lack of recent contact with a family doctor and current smoking were independently associated with non-vaccination. Discussion Influenza vaccination helps prevent severe influenza outcomes. Yet, half of adults aged 46–64 years with ≥1 CMC and more than one-quarter of all adults aged ≥65 years did not receive a recommended influenza vaccine in the year prior to the survey. Innovation in vaccination campaigns for routinely recommended vaccines, especially among those without annual family doctor visits, may improve coverage. Conclusion Influenza vaccination coverage among Canadian adults aged 46–64 years with ≥1 CMC and adults aged ≥65 years remains suboptimal. Vaccination campaigns targeting those at high risk of severe outcomes without routine physician engagement should be evaluated to improve uptake.

BackgroundWe assessed the impact of the coronavirus disease 2019 (COVID-19) epidemic in India on the consumption of antibiotics and hydroxychloroquine (HCQ) in the private sector in 2020 compared to the expected level of use had the epidemic not occurred.Methods and findingsWe performed interrupted time series (ITS) analyses of sales volumes reported in standard units (i.e., doses), collected at regular monthly intervals from January 2018 to December 2020 and obtained from IQVIA, India. As children are less prone to develop symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a predominant increase in non-child-appropriate formulation (non-CAF) sales. COVID-19-attributable changes in the level and trend of monthly sales of total antibiotics, azithromycin, and HCQ were estimated, accounting for seasonality and lockdown period where appropriate. A total of 16,290 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. However, the proportion of non-CAF antibiotics increased from 72.5% (95% CI: 71.8% to 73.1%) in 2019 to 76.8% (95% CI: 76.2% to 77.5%) in 2020. Our ITS analyses estimated that COVID-19 likely contributed to 216.4 million (95% CI: 68.0 to 364.8 million; P = 0.008) excess doses of non-CAF antibiotics and 38.0 million (95% CI: 26.4 to 49.2 million; P < 0.001) excess doses of non-CAF azithromycin (equivalent to a minimum of 6.2 million azithromycin treatment courses) between June and September 2020, i.e., until the peak of the first epidemic wave, after which a negative change in trend was identified. In March 2020, we estimated a COVID-19-attributable change in level of +11.1 million doses (95% CI: 9.2 to 13.0 million; P < 0.001) for HCQ sales, whereas a weak negative change in monthly trend was found for this drug. Study limitations include the lack of coverage of the public healthcare sector, the inability to distinguish antibiotic and HCQ sales in inpatient versus outpatient care, and the suboptimal number of pre- and post-epidemic data points, which could have prevented an accurate adjustment for seasonal trends despite the robustness of our statistical approaches.ConclusionsA significant increase in non-CAF antibiotic sales, and particularly azithromycin, occurred during the peak phase of the first COVID-19 epidemic wave in India, indicating the need for urgent antibiotic stewardship measures.

Introduction Although universal drug susceptibility testing (DST) is a component of the End-TB Strategy, over 70% of drug-resistant tuberculosis (DR-TB) cases globally remain undetected. This detection gap reflects difficulties in DST scale-up and substantial heterogeneity in policies and implemented practices. We conducted a systematic review and meta-analysis to assess whether implementation of universal DST yields increased DR-TB detection compared with only selectively testing high-risk groups.Methods PubMed, Embase, Global Health, Cochrane Library and Web of Science Core Collection were searched for publications reporting on the differential yield of universal versus selective DST implementation on the proportion of DR-TB, from January 2007 to June 2019. Random-effects meta-analyses were used to calculate respective pooled proportions of DR-TB cases detected; Higgins test and prediction intervals were used to assess between-study heterogeneity. We adapted an existing risk-of-bias assessment tool for prevalence studies.Results Of 18 736 unique citations, 101 studies were included in the qualitative synthesis. All studies used WHO-endorsed DST methods, and most (87.1%) involved both high-risk groups and the general population. We found only cross-sectional, observational, non-randomised studies that compared universal with selective DST strategies. Only four studies directly compared the testing approaches in the same study population, with the proportion of DR-TB cases detected ranging from 2.2% (95% CI: 1.4% to 3.2%) to 12.8% (95% CI: 11.4% to 14.3%) with selective testing, versus 4.4% (95% CI: 3.3% to 5.8%) to 9.8% (95% CI: 8.9% to 10.7%) with universal testing. Broad population studies were very heterogeneous. The vast majority (88/101; 87.1%) reported on the results of universal testing. However, while 37 (36.6%)/101 included all presumptive TB cases, an equal number of studies applied sputum-smear as a preselection criterion. A meaningful meta-analysis was not possible.Conclusion Given the absence of randomised studies and the paucity of studies comparing strategies head to head, and selection bias in many studies that applied universal testing, our findings have limited generalisability. The lack of evidence reinforces the need for better data to inform policies.

Introduction Determining whether antibiotic prescriptions are inappropriate requires knowledge of patients’ underlying conditions. In low-income and middle-income countries (LMICs), where misdiagnoses are frequent, this is challenging. Additionally, such details are often unavailable for prescription audits. Recent studies using standardised patients (SPs) offer a unique opportunity to generate unbiased prevalence estimates of antibiotic overuse, as the research design involves patients with predefined conditions.Methods Secondary analyses of data from nine SP studies were performed to estimate the proportion of SP–provider interactions resulting in inappropriate antibiotic prescribing across primary care settings in three LMICs (China, India and Kenya). In all studies, SPs portrayed conditions for which antibiotics are unnecessary (watery diarrhoea, presumptive tuberculosis (TB), angina and asthma). We conducted descriptive analyses reporting overall prevalence of antibiotic overprescribing by healthcare sector, location, provider qualification and case. The WHO Access–Watch–Reserve framework was used to categorise antibiotics based on their potential for selecting resistance. As richer data were available from India, we examined factors associated with antibiotic overuse in that country through hierarchical Poisson models.Results Across health facilities, antibiotics were given inappropriately in 2392/4798 (49.9%, 95% CI 40.8% to 54.5%) interactions in India, 83/166 (50.0%, 95% CI 42.2% to 57.8%) in Kenya and 259/899 (28.8%, 95% CI 17.8% to 50.8%) in China. Prevalence ratios of antibiotic overuse in India were significantly lower in urban versus rural areas (adjusted prevalence ratio (aPR) 0.70, 95% CI 0.52 to 0.96) and higher for qualified versus non-qualified providers (aPR 1.55, 95% CI 1.42 to 1.70), and for presumptive TB cases versus other conditions (aPR 1.19, 95% CI 1.07 to 1.33). Access antibiotics were predominantly used in Kenya (85%), but Watch antibiotics (mainly quinolones and cephalosporins) were highly prescribed in India (47.6%) and China (32.9%).Conclusion Good-quality SP data indicate alarmingly high levels of antibiotic overprescription for key conditions across primary care settings in India, China and Kenya, with broad-spectrum agents being excessively used in India and China.

BackgroundThe widespread use of antibiotics plays a major role in the development and spread of antimicrobial resistance. However, important knowledge gaps still exist regarding the extent of their use in low- and middle-income countries (LMICs), particularly at the primary care level. We performed a systematic review and meta-analysis of studies conducted in primary care in LMICs to estimate the prevalence of antibiotic prescriptions as well as the proportion of such prescriptions that are inappropriate.Methods and findingsWe searched PubMed, Embase, Global Health, and CENTRAL for articles published between 1 January 2010 and 4 April 2019 without language restrictions. We subsequently updated our search on PubMed only to capture publications up to 11 March 2020. Studies conducted in LMICs (defined as per the World Bank criteria) reporting data on medicine use in primary care were included. Three reviewers independently screened citations by title and abstract, whereas the full-text evaluation of all selected records was performed by 2 reviewers, who also conducted data extraction and quality assessment. A modified version of a tool developed by Hoy and colleagues was utilized to evaluate the risk of bias of each included study. Meta-analyses using random-effects models were performed to identify the proportion of patients receiving antibiotics. The WHO Access, Watch, and Reserve (AWaRe) framework was used to classify prescribed antibiotics. We identified 48 studies from 27 LMICs, mostly conducted in the public sector and in urban areas, and predominantly based on medical records abstraction and/or drug prescription audits. The pooled prevalence proportion of antibiotic prescribing was 52% (95% CI: 51%-53%), with a prediction interval of 44%-60%. Individual studies' estimates were consistent across settings. Only 9 studies assessed rationality, and the proportion of inappropriate prescription among patients with various conditions ranged from 8% to 100%. Among 16 studies in 15 countries that reported details on prescribed antibiotics, Access-group antibiotics accounted for more than 60% of the total in 12 countries. The interpretation of pooled estimates is limited by the considerable between-study heterogeneity. Also, most of the available studies suffer from methodological issues and report insufficient details to assess appropriateness of prescription.ConclusionsAntibiotics are highly prescribed in primary care across LMICs. Although a subset of studies reported a high proportion of inappropriate use, the true extent could not be assessed due to methodological limitations. Yet, our findings highlight the need for urgent action to improve prescription practices, starting from the integration of WHO treatment recommendations and the AWaRe classification into national guidelines.Trial registrationPROSPERO registration number: CRD42019123269.

Giorgia Sulis and Madhukar Pai discuss the global distribution, and approaches to diagnosis and treatment, of isoniazid-resistant tuberculosis.

Background Antimicrobial resistance is a global health emergency, and one of the contributing factors is overuse and misuse of antibiotics. India is one of the world’s largest consumers of antibiotics, and inappropriate use is potentially widespread. This study aimed to use standardised patients (SPs) to measure over-the-counter antibiotic dispensing in one region.Methods Three adults from the local community in Udupi, India, were recruited and trained as SPs. Three conditions, in both adults and children, were considered: diarrhoea, upper respiratory tract infection and acute fever. Adult SPs were used as proxies for the paediatric cases.Results A total of 1522 SP interactions were successfully completed from 279 pharmacies. The proportion of SP interactions resulting in the provision of an antibiotic was 4.34% (95% CI 3.04% to 6.08%) for adult SPs and 2.89% (95% CI 1.8% to 4.4%) for child SPs. In the model, referral to another provider was associated with an OR 0.38 (95% CI 0.18 to 0.79), the number of questions asked was associated with an OR 1.54 (95% CI 1.30 to 1.84) and an SP–pharmacist interaction lasting longer than 3 min was associated with an OR 3.03 (95% CI 1.11 to 8.27) as compared with an interaction lasting less than 1 min.Conclusion Over-the-counter antibiotic dispensing rate was low in Udupi district and substantially lower than previously published SP studies in other regions of India. Dispensing was lowest when pharmacies referred to a doctor, and higher when pharmacies asked more questions or spent more time with clients.

Globally 10.4 million new tuberculosis (TB) incident cases were estimated to have occurred in 2015, of which 3% were reported in the World Health Organization European Region. Importantly, about 25% of the global multidrug-resistant TB (MDR-TB) cases are reported in the European Region, representing one of the greatest challenges to TB control; these are reported particularly in the countries of the Former Soviet Union. Over a quarter of TB cases in the European Union and European Economic Area (EU/EEA) are reported among foreign-born individuals. In line with the recent increase of migration flows towards Europe, TB among migrant populations is also on the rise, emphasizing the need for a better understanding of the TB trends at the regional and sub-regional levels, and of the existing policies on migrants and refugees. The present article is aimed at describing the policies and practices of European countries with a low and intermediate TB incidence with regard to the detection and management of TB and latent TB infection (LTBI) among refugees in Europe.

Abstract Background We carried out a study to evaluate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae genital infections in school-based adolescents in Northern Italy. Methods Systematic screening for C. trachomatis and N. gonorrhoeae genital infection was performed in 13th grade students in the province of Brescia, an industrialized area in Northern Italy. Student filled in a questionnaire on sexual behaviour and provided a urine sample for microbiological testing. Results A total of 2,718 students (mean age: 18.4 years; 59.1 % females) provided complete data (62.2 % of those eligible). Overall 2,059 students (75.8 %) were sexually active (i.e. had had at least one partner), and the mean age at sexual debut was 16.1 years (SD: 1.4). Only 27.5 % of the sexually active students reported regular condom use during the previous 6 months, with higher frequency in males than in females (33.8 % vs 24.2 %). No case of N. gonorrhoeae infection was detected, while C. trachomatis was found in 36 adolescents, with a prevalence of 1.7 % (95 % CI: 1.2–2.4) among sexually active students, and no statistical difference between females and males (1.9 and 1.4 %, respectively). Inconsistent condom use (odds ratio, OR = 5.5) and having had more than one sexual partner during the previous 6 months (OR = 6.8) were associated with an increased risk of Chlamydia infection at multivariate analysis. Conclusion The prevalence of C. trachomatis infection among sexually active adolescents in Northern Italy was low, despite a high proportion of students who engage in risky sexual behaviour. No cases of N. gonorrhoeae infection were identified.

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide, accounting for about 9.6 million new cases and 1.5 million deaths annually. The poorest and socially excluded groups carry the largest burden of disease, which makes it essential to properly address the social determinants of health through poverty reduction measures and targeted interventions on high-risk populations. The spread of multidrug-resistance TB requires special attention and highlights the need to foster research on TB diagnostics, new drugs and vaccines. Although many advances have been made in the fight against TB over the last twenty years, a lot is still needed to achieve global elimination. The new end-TB strategy that was first launched in 2014 by the World Health Organization, is fully in line with the seventeen Sustainable Development Goals that came into effect since January 2016 and sets ambitious goals for the post-2015 agenda. A 90% reduction in TB-related mortality and an 80% decline in TB incidence within 2030 as well as the abolition of catastrophic expenditures for TB-affected people are the main targets of this strategy. Strong government commitment and adequate financing from all countries together with community engagement and appropriate investments in research are necessary in order to reach these objectives.

Tuberculosis (TB) is a major public health concern worldwide: despite a regular, although slow, decline in incidence over the last decade, as many as 8.6 million new cases and 1.3 million deaths were estimated to have occurred in 2012. TB is by all means a poverty-related disease, mainly affecting the most vulnerable populations in the poorest countries. The presence of multidrug-resistant strains of M. tuberculosis in most countries, with some where prevalence is high, is among the major challenges for TB control, which may hinder recent achievements especially in some settings. Early TB case detection especially in resource-constrained settings and in marginalized groups remains a challenge, and about 3 million people are estimated to remain undiagnosed or not notified and untreated. The World Health Organization (WHO) has recently launched the new global TB strategy for the “post-2015 era” aimed at “ending the global TB epidemic” by 2035, based on the three pillars that emphasize patient-centred TB care and prevention, bold policies and supportive systems, and intensified research and innovation. This paper aims to provide an overview of the global TB epidemiology as well as of the main challenges that must be faced to eliminate the disease as a public health problem everywhere.