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IntroductionAlthough 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.MethodsPubMed, 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.ResultsOf 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.ConclusionGiven 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.

IntroductionDetermining 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.MethodsSecondary 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.ResultsAcross 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%).ConclusionGood-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.

BACKGROUND: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely passive, which impedes epidemic control. We defined active testing strategies for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) for groups at increased risk of acquiring SARS-CoV-2 in all Canadian provinces. METHODS: We identified 5 groups who should be prioritized for active RT-PCR testing: contacts of people who are positive for SARS-CoV-2, and 4 at-risk populations — hospital employees, community health care workers and people in long-term care facilities, essential business employees, and schoolchildren and staff. We estimated costs, human resources and laboratory capacity required to test people in each group or to perform surveillance testing in random samples. RESULTS: During July 8–17, 2020, across all provinces in Canada, an average of 41 751 RT-PCR tests were performed daily; we estimated this required 5122 personnel and cost $2.4 million per day ($67.8 million per month). Systematic contact tracing and testing would increase personnel needs 1.2-fold and monthly costs to $78.9 million. Conducted over a month, testing all hospital employees would require 1823 additional personnel, costing $29.0 million; testing all community health care workers and persons in long-term care facilities would require 11 074 additional personnel and cost $124.8 million; and testing all essential employees would cost $321.7 million, requiring 25 965 added personnel. Testing the larger population within schools over 6 weeks would require 46 368 added personnel and cost $816.0 million. Interventions addressing inefficiencies, including saliva-based sampling and pooling samples, could reduce costs by 40% and personnel by 20%. Surveillance testing in population samples other than contacts would cost 5% of the cost of a universal approach to testing at-risk populations. INTERPRETATION: Active testing of groups at increased risk of acquiring SARS-CoV-2 appears feasible and would support the safe reopening of the economy and schools more broadly. This strategy also appears affordable compared with the $169.2 billion committed by the federal government as a response to the pandemic as of June 2020.

Background The 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 findings We 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. Conclusions Antibiotics 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 registration PROSPERO registration number: CRD42019123269., Giorgia Sulis and colleagues report the prevalence of antibiotic prescriptions in primary care in low-middle income countries in a systematic review and meta-analysis., Author summary Why was this study done? Inappropriate use of antibiotics, both in terms of incorrect regimens and prescription without clinical indication, is a major driver of antibiotic resistance. Global drug sales data indicate a substantial increase in antibiotic use in low- and middle-income countries (LMICs) over the past 2 decades. An accurate quantification of antibiotic prescribing in primary care across LMICs is not available. What did the researchers do and find? We conducted a systematic review and meta-analysis to estimate the proportion of antibiotic prescribing across primary care settings in LMICs. Our study showed that, on average, approximately half of patients attending primary care facilities in LMICs received at least 1 antibiotic. Very few included studies made an attempt to assess the extent of inappropriate prescriptions and indicate potential misuse. Among studies that provided information on the types of antibiotics used, we found that, in 12/16 studies, 60% of prescriptions were for antibiotics with low potential for resistance selection as defined by the World Health Organization (WHO). What do these findings mean? Our study highlights that antibiotics are highly prescribed in outpatient primary care settings. Better quality data are necessary to dig deeper into the patterns of inappropriate use according to local epidemiologic scenarios. Adapting WHO treatment recommendations and incorporating the WHO Access, Watch, and Reserve (AWaRe) classification of antibiotics into national guidelines will be a first key step to improve prescription practices.

BackgroundThis 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.MethodsThis 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.ResultsThe Cmax and AUC0–12hmedians 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.ConclusionThis 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 registrationPACTR201310000629390, 28th October 2013.

Background The surveillance of drug resistance among tuberculosis (TB) patients is central to combatting the global TB epidemic and preventing the spread of antimicrobial resistance. Isoniazid and rifampicin are two of the most powerful first-line anti-TB medicines, and resistance to either of them increases the risk of treatment failure, relapse, or acquisition of resistance to other drugs. The global prevalence of rifampicin resistance is well documented, occurring in 3.4% (95% CI 2.5%–4.4%) of new TB patients and 18% (95% CI 7.6%–31%) of previously treated TB patients in 2018, whereas the prevalence of isoniazid resistance at global and regional levels is less understood. In 2018, the World Health Organization (WHO) recommended a modified 6-month treatment regimen for people with isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), which includes rifampicin, pyrazinamide, ethambutol, and levofloxacin. We estimated the global prevalence of Hr-TB among TB patients and investigated associated phenotypic and genotypic drug resistance patterns. Methods and findings Aggregated drug resistance data reported to WHO from either routine continuous surveillance or nationally representative periodic surveys of TB patients for the period 2003–2017 were reviewed. Isoniazid data were available from 156 countries or territories for 211,753 patients. Among these, the global prevalence of Hr-TB was 7.4% (95% CI 6.5%–8.4%) among new TB patients and 11.4% (95% CI 9.4%–13.4%) among previously treated TB patients. Additional data on pyrazinamide and levofloxacin resistance were available from 6 countries (Azerbaijan, Bangladesh, Belarus, Pakistan, the Philippines, and South Africa). There were no cases of resistance to both pyrazinamide and levofloxacin among Hr-TB patients, except for the Philippines (1.8%, 95% CI 0.2–6.4) and Belarus (5.3%, 95% CI 0.1–26.0). Sequencing data for all genomic regions involved in isoniazid resistance were available for 4,563 patients. Among the 1,174 isolates that were resistant by either phenotypic testing or sequencing, 78.6% (95% CI 76.1%–80.9%) had resistance-conferring mutations in the katG gene and 14.6% (95% CI 12.7%–16.8%) in both katG and the inhA promoter region. For 6.8% (95% CI 5.4%–8.4%) of patients, mutations occurred in the inhA promoter alone, for whom an increased dose of isoniazid may be considered. The main limitations of this study are that most analyses were performed at the national rather than individual patient level and that the quality of laboratory testing may vary between countries. Conclusions In this study, the prevalence of Hr-TB among TB patients was higher than the prevalence of rifampicin resistance globally. Many patients with Hr-TB would be missed by current diagnostic algorithms driven by rifampicin testing, highlighting the need for new rapid molecular technologies to ensure access to appropriate treatment and care. The low prevalence of resistance to pyrazinamide and fluoroquinolones among patients with Hr-TB provides further justification for the recommended modified treatment regimen., Anna Dean and colleagues study patterns of isoniazid resistance in tuberculosis patients across 156 countries or territories., Author summary Why was this study done? Tuberculosis (TB) is the leading cause of death from an infectious disease, with 1.2 million deaths occurring in 2018. People infected with a TB strain that is resistant to standard medicines used for treatment, including rifampicin or isoniazid, have a lower chance of being cured and a higher risk of death. In 2018, the World Health Organization (WHO) recommended a modified treatment regimen for patients with TB that is resistant to isoniazid but susceptible to rifampicin (Hr-TB). What did the researchers do and find? Data reported from 156 countries or territories to WHO between 2002 and 2018 were used to determine that a relatively high proportion of TB patients had Hr-TB: 7.4% (95% CI 6.5%–8.4%) of new patients and 11.4% (95% CI 9.4%–13.4%) of previously treated patients. In 6 countries with testing results for other medicines that are recommended in the modified treatment regimen (pyrazinamide and levofloxacin), resistance among Hr-TB patients was uncommon. Combined resistance to both drugs was only detected in the Philippines and Belarus but not in Azerbaijan, Bangladesh, Pakistan, or South Africa. Data from whole genome sequencing were also used to investigate markers of isoniazid resistance in 6 countries (Azerbaijan, Belarus, Bangladesh, Pakistan, South Africa and Ukraine). What do these findings mean? The modified treatment regimen recommended by WHO in 2018 for Hr-TB patients is likely to be effective in many settings. However, many patients with Hr-TB are missed because of the lack of laboratory capacity in many countries to screen for isoniazid resistance and the absence of appropriate diagnostic tools.

Background We 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 findings We 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. Conclusions A 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., Giorgia Sulis and co-workers analyze sales of antimicrobials and hydroxchloroquine in India during 2018-20 to assess possible changes across the COVID-19 epidemic., Author summary Why was this study done? There are concerns that the widespread and often inappropriate use of antibiotics has been aggravated by the COVID-19 pandemic, but little is known regarding the true impact of the pandemic on antibiotic use, particularly in low- and middle-income countries (LMICs). India is the largest antibiotic user in the world and is among the countries that are most severely affected by the pandemic. About 75% of healthcare in India is private, and this unregulated and fragmented private sector accounts for 90% of antibiotic consumption, raising major concerns about the potential effects of COVID-19 on prescribing and dispensing practices. What did the researchers do and find? Using an interrupted time series (ITS) design, we examined sales volumes of total antibiotics, azithromycin alone, and hydroxychloroquine (HCQ) in India’s private sector from January 2018 to December 2020. Focusing on non-pediatric formulations and adjusting for underlying seasonal and non-seasonal trends and accounting for the effect of lockdown, we estimated the impact of the first epidemic wave on monthly sales. Based on our models, COVID-19 likely contributed to about 216 million excess doses (95% CI: 68.0 to 364.8 million; P = 0.008) of total antibiotics and 38.0 million excess doses (95% CI: 26.4 to 49.2 million; P < 0.001) of azithromycin between June and September 2020 (i.e., after the lockdown and until the epidemic peak). HCQ sales peaked in March 2020, reflecting the widespread use of this drug for both prophylaxis and treatment of COVID-19 (+11.1 million doses [95% CI: 9.2 to 13.0 million]; P < 0.001), followed by a slow decline afterwards. What do these findings mean? Our findings indicate a significant increase in antibiotic sales, particularly of azithromycin, during the peak phase of the first COVID-19 epidemic wave in India. Similar trends are likely to have occurred in other LMICs, where antibiotics are often overused. The medium- and long-term consequences for bacterial resistance patterns are highly concerning, highlighting the need for urgent antibiotic stewardship measures.

Latent tuberculosis infection (LTBI) affects one third to one fourth of the human population and is the reservoir for a significant proportion of emerging active tuberculosis (TB) cases, especially in low incidence countries. The World Health Organization launched in 2015 the END-TB strategy that aims at TB elimination and promotes, for the first time ever, the management of LTBI. The preventive package, basically consisting of testing and treatment for LTBI in groups at high risk of reactivation, is a mainstay of the first pillar of the strategy, alongside prompt diagnosis and early treatment of both drug-susceptible and drug-resistant TB disease. Testing and treatment for LTBI should be pursued with a programmatic perspective. This implies strong political commitment, adequate funding and an effective monitoring and evaluation system. People living with HIV and children under five years of age who are household contact of a contagious TB cases are primarily targeted in all epidemiological setting. In high resource and low incidence setting, additional at risk populations should also be the target for systematic LTBI testing and treatment. Research is urgently needed to develop diagnostic tests with higher predictive value to identify individuals that progress from infection to disease. Similarly, shorter and safer treatment regimens are needed to make the trade-off between potential benefits and harms more favourable for an increasing proportion of infected individuals.

BackgroundTo 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.MethodsThis 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.ResultsThe medians LPV Cmaxand Tmaxwere 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 AUC0–12of 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 C0of 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 AUC0–12of RTV in arm A was 12.7 μg h/mL versus 6.6 μg h/ml in arm B (p = 0.313).ConclusionIn 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 registrationPACTR201310000629390. Registered 28 October 2013,http://www.pactr.org/

Invasive collection methods are often required to obtain samples for the microbiological evaluation of children with presumptive pulmonary tuberculosis (PTB). Nucleic acid amplification testing of easier-to-collect stool samples could be a noninvasive method of diagnosing PTB., Invasive collection methods are often required to obtain samples for the microbiological evaluation of children with presumptive pulmonary tuberculosis (PTB). Nucleic acid amplification testing of easier-to-collect stool samples could be a noninvasive method of diagnosing PTB. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of testing stool with the Xpert MTB/RIF assay (“stool Xpert”) for childhood PTB. Four databases were searched for publications from January 2008 to June 2018. Studies assessing the diagnostic accuracy among children of stool Xpert compared to a microbiological reference standard of conventional specimens tested by mycobacterial culture or Xpert were eligible. Bivariate random-effects meta-analyses were performed to calculate pooled sensitivity and specificity of stool Xpert against the reference standard. From 1,589 citations, 9 studies (n = 1,681) were included. Median participant ages ranged from 1.3 to 10.6 years. Protocols for stool processing and testing varied substantially, with differences in reagents and methods of homogenization and filtering. Against the microbiological reference standard, the pooled sensitivity and specificity of stool Xpert were 67% (95% confidence interval [CI], 52 to 79%) and 99% (95% CI, 98 to 99%), respectively. Sensitivity was higher among children with HIV (79% [95% CI, 68 to 87%] versus 60% [95% CI, 44 to 74%] among HIV-uninfected children). Heterogeneity was high. Data were insufficient for subgroup analyses among children under the age of 5 years, the most relevant target population. Stool Xpert could be a noninvasive method of ruling in PTB in children, particularly those with HIV. However, studies focused on children under 5 years of age are needed, and generalizability of the evidence is limited by the lack of standardized stool preparation and testing protocols.

Tuberculosis (TB) is still a major public health concern, mostly affecting resource-constrained settings and marginalized populations. The fight against the disease is hindered by the growing emergence of drug-resistant forms whose management can be rather challenging. Surgery may play an important role to support diagnosis and treatment of the most complex cases and improve their therapeutic outcome. We conducted a non-systematic review of the literature based on relevant keywords through PubMed database. Papers in English and Russian were included. The search was focused on five main areas of intervention as follows: (I) diagnosis of complicated cases; (II) elimination of contagious persisting cavities, despite appropriate chemotherapy; (III) treatment of destroyed lung; (V) resection of tuberculomas; (VI) treatment of tuberculous pleural empyema. Although specific practical guidelines concerning surgical indications and approaches are currently unavailable, a summary of the evidence emerged from the scientific literature was elaborated to help the clinician in the management of severely compromised TB patients. The decision to proceed to surgery is usually individualized and a careful assessment of the patient’s risk profile is always recommended before performing any procedure in addition to appropriate chemotherapy.

No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanateversusmeropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanateversusmeropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases.84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8versus8) but more fluoroquinolone resistance (79.0%versus48.9%, pversus49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60–428)versus85 (49–156) days, respectively.Statistically significant differences were observed on sputum smear and culture conversion rates (79.7%versus94.8%, p=0.02 and 71.9%versus94.8%, pversus77.5%, p=0.03). Adverse events to imipenem/clavulanate and meropenem/clavulanate were reported in 5.4% and 6.5% of cases only.Our study suggests that meropenem/clavulanate is more effective than imipenem/clavulanate in treating MDR/XDR-TB patients.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-2839-x) contains supplementary material, which is available to authorized users.

There has been much speculation during the past week about the catastrophe that awaits once coronavirus disease 2019 (COVID-19) establishes itself in the poorest communities of South Africa (SA) and, importantly, in informal settlements. Evidence to date suggests that COVID-19 is efficiently passed from infected individuals via large droplets and hard-surface fomites.

The number of international migrants worldwide has continued to grow rapidly over the past fifteen years and the trend is expected to continue, making the health matters associated with migration a crucial public health challenges faced by governments and societies. Multidrug-resistant tuberculosis is a paradigm of transmissible diseases that do not respect borders and poses a multifaceted and complex challenge on migrant health. The guiding principles for the health response are the respect of equity and human rights as well as the accurate analysis of epidemiological trends and determinants of TB in migrants. The action framework “Towards tuberculosis elimination: an action framework for low-incidence countries” includes regulations for cross border migration among the top eight interventions for TB elimination in low incidence countries. Political commitment is the essential requirement, and currently, the limiting factor, to draft regulations for cross-border collaboration, establish cross-border referral systems with contact tracing and information sharing. The e-platform TB Consilium hosted by European Respiratory Society in collaboration with World Health Organization – Euro is an example of a tool that can be used to exchange information for clinical management and surveillance.

BACKGROUND Although the management of latent tuberculous infection (LTBI) is a core component of the End TB Strategy, there is limited information about the status of implementation of such interventions in most African countries. METHODS A web-based survey involving the 47 countries of the African Region was conducted between November 2016 and April 2017. RESULTS The questionnaire was completed by 32/47 (68.1%) National TB Programme managers or their delegates. LTBI guidelines were available in four countries (12.5%), while 13 (40.6%) had an LTBI section in their national TB guidelines; there was no significant association with socio-economic conditions and funding allocation. LTBI diagnosis was mostly based on clinical evaluation to rule out active disease, rather than on systematic use of the tuberculin skin test. Respectively 23 (71.8%) and 17 countries (53.1%) reported providing treatment to child contacts aged

To develop and test a simple system for recording and reporting the diagnosis and treatment of latent tuberculosis infection and to compare the effects of passive and active tracing of child contacts on indicators of such infection.We revised Burkina Faso's latent tuberculosis infection register and quarterly tuberculosis reporting form. Subsequently, coverage of the routine screening of contacts, who were younger than five years, for active tuberculosis and the corresponding percentages of such contacts who, if eligible, initiated preventive therapy were measured, nationwide, between 1 April 2016 and 31 March 2017. In 2016, we evaluated indicators of latent tuberculosis infection in the Hauts-Bassins region before and after community health workers had begun the active tracing of contacts who were younger than five years.In Burkina Faso, during our study period, 3717 cases of pulmonary tuberculosis and 1166 corresponding contacts who were younger than five years were reported as the result of routine screening and passive contact tracing. The overall contact:index ratio was 0.31 and corresponding screening coverage was 82.0% (956/1166) and proportion of children starting on preventive treatment was 90.5% (852/941). Active tracing in Hauts-Bassins led to a substantially higher contact/index ratio (1.83) and screening coverage (99.3%; 145/146).The newly established recording and reporting system proved feasible and user-friendly and allowed measurement of global indicators of latent tuberculosis infection. Compared with active tracing, passive tracing led to much lower estimates of the numbers of child contacts.Élaborer et tester un système simple pour enregistrer et déclarer le diagnostic et le traitement des cas d'infection tuberculeuse latente et comparer les effets de la recherche passive et active des contacts enfants sur les indicateurs de cette infection.Nous avons passé en revue le registre des infections tuberculeuses latentes et le formulaire de rapport trimestriel des cas de tuberculose du Burkina Faso. Ensuite, nous avons mesuré, dans tout le pays, entre le 1Au Burkina Faso, au cours de la période étudiée, 3717 cas de tuberculose pulmonaire et 1166 contacts correspondants âgés de moins de cinq ans ont été déclarés dans le cadre du dépistage systématique et de la recherche passive des contacts. Le ratio total contacts/cas index était de 0,31 et le taux de couverture du dépistage correspondant s'élevait à 82,0% (956/1166), tandis que la proportion d'enfants ayant commencé un traitement préventif était de 90,5% (852/941). La recherche active dans les Hauts-Bassins a entraîné une hausse sensible du ratio total contacts/cas index (1,83) et du taux de couverture du dépistage (99,3%; 145/146).Le nouveau système d'enregistrement et de déclaration s'est avéré utilisable et convivial et a permis de mesurer les indicateurs globaux de l'infection tuberculeuse latente. En comparaison avec la recherche active, la recherche passive a généré des estimations beaucoup plus faibles du nombre de contacts enfants.Desarrollar y probar un sistema simple de registro y presentación de informes sobre el diagnóstico y el tratamiento de la infección tuberculosa latente y comparar los efectos del seguimiento pasivo y activo de los contactos infantiles con indicadores de dicha infección.Se revisó el registro de infección tuberculosa latente de Burkina Faso y el formulario trimestral de información sobre la tuberculosis. Posteriormente, se midió la cobertura de los exámenes de detección rutinarios a los contactos, menores de cinco años, para la tuberculosis activa y los porcentajes correspondientes de contactos que, de ser aptos, iniciaron la terapia preventiva a nivel nacional, entre el 1 de abril de 2016 y el 31 de marzo de 2017. En 2016, se evaluaron los indicadores de infección tuberculosa latente en la región de Hauts-Bassins antes y después de que los trabajadores comunitarios de la salud empezaran el seguimiento activo de los contactos menores de cinco años.En Burkina Faso, en nuestro periodo de estudio, se registraron 3717 casos de tuberculosis pulmonar y 1166 contactos correspondientes de menos de cinco años como resultado de un examen rutinario y un seguimiento del contacto pasivo. La tasa global de índice de contacto fue del 0,31 y la cobertura de detección correspondiente fue del 82,0% (956/1166), además, la proporción de niños que iniciaron el tratamiento preventivo fue del 90,5% (852/941). El seguimiento activo en Hauts-Bassins dio lugar a una relación de contacto/índice (1,83) y una cobertura de detección (99,3%; 145/146) sustancialmente más altas.El recién establecido sistema simple de registro y presentación de informes resultó factible y fácil de usar y permitió la medición de indicadores globales de la infección tuberculosa latente. En comparación con el seguimiento activo, el seguimiento pasivo dio lugar a estimaciones mucho más bajas de la cantidad de contactos secundarios.وضع واختبار نظام بسيط للتسجيل والإبلاغ عن حالات تشخيص وعلاج العدوى الكامنة بداء السل، ومقارنة آثار التتبع السلبي والنشط لحالات تعرض الأطفال إلى المرض بمؤشرات تلك العدوى.لقد راجعنا سجل الإصابة بداء السل الكامن في بوركينا فاصو، ونموذج البلاغات ربع السنوية للإصابة بداء السل. وبعد ذلك، تم قياس حجم تغطية الفحص الدوري لحالات الاتصال بالمرض بين الأطفال دون سن خمس سنوات للكشف عن حالات الإصابة النشطة بداء السل وما يقابلها من نسب الاتصال بالمرض بين الأطفال الذين شرعوا في تعاطي العلاج الوقائي إذا كانوا مؤهلين له، وذلك على مستوى البلاد في الفترة ما بين 1 أبريل/نيسان 2016 و31 مارس/آذار 2017. وفي عام 2016، قمنا بتقييم مؤشرات الإصابة بداء السل الكامن في منطقة أوت باسان قبل وبعد قيام الأخصائيين الصحيين المجتمعيين بالبدء في عمليات التتبع النشط لحالات الاتصال بالمرض بين الأطفال الذين تقل أعمارهم عن خمس سنوات.في بوركينا فاصو، تم الإبلاغ عن 3717 حالة للإصابة بداء السل الرئوي و1166 حالة مقابلة من الاتصال بالمرض بين الأطفال الأقل من خمس سنوات – كنتيجة للفحص الدوري وعمليات التتبع السلبي – وذلك خلال فترة الدراسة. وبلغت النسبة الإجمالية لحالات التعرض للمرض إلى مؤشر الإصابة 0.31، أما النسبة المقابلة لشمول خدمات الفحص فبلغت نسبتها 82.0‏% (بواقع ‏956/1166)، وبلغت نسبة الأطفال الذين بدأوا العلاج الوقائي 90.5‏% (852/941). وقادت عمليات التتبع النشط في منطقة أوت باسان إلى ارتفاع ملحوظ في نسبة حالات التعرض للمرض إلى مؤشر الإصابة (1.83)، أما نسبة شمول خدمات الفحص فبلغت (99.3‏%؛ 145/146).أثبت النظام الذي تم تأسيسه مؤخرًا لتسجيل حالات الإصابة وتقديم البلاغات عنها جدواه وسهولة استخدامه، وسمح بقياس المؤشرات العالمية لحالات العدوى الكامنة بداء السل. وبالمقارنة مع عمليات التتبع النشط، فقد قاد التتبع السلبي إلى تقديرات أقل كثيرًا لأعداد الأطفال الذين تعرضوا إلى الاتصال بالمرض.研发并测试一个简易系统，用于记录和报告潜在结核病感染的诊断与治疗，并对此类感染指标下针对儿童接触者分别进行被动追踪和主动追踪的效果进行比较。.我们修订了布基纳法索潜在结核病感染登记和季度结核病申报表。随后，在 2016 年 4 月 1 日至 2017 年 3 月 31 日之间，针对年龄不足 5 岁的活动性结核病患者进行常规性筛查并对此类符合条件的接触者开始实施预防性治疗，分别测量其在全国范围内的覆盖率和相应的百分比。2016 年，我们先评估了上盆地大区潜在结核病感染指标，之后，社区健康工作者开始积极追踪年龄不足 5 岁的儿童接触者。.在我们研究期间，经过常规性筛查和被动接触追踪，据报告称，布基纳法索有 3717 例结核病案例和 1166 位年龄不足 5 岁的相应接触者。总体接触指数比为 0.31，相应的筛查覆盖率为 82.0%（956/1166)，开始预防性治疗的儿童比例为 90.5%（852/941)。对上盆地大区的结核病积极追踪导致更高的接触指数比 （1.83） 和筛查覆盖率 （99.3%，145/146）。.新建立的记录报告系统被证明行之有效且用户友好，其可以评估潜伏结核病感染的全球指标。与积极追踪相比，消极追踪会造成对儿童接触者数量的低估。.Разработать и протестировать простую систему регистрации и отчетности для диагностики и лечения латентной туберкулезной инфекции и сравнить влияние пассивного и активного отслеживания детей, находившихся в контакте с инфицированным человеком, на показатели такой инфекции.Авторы изучили реестр лиц, больных латентным туберкулезом, в Буркина-Фасо и ежеквартальную форму отчетности о количестве больных туберкулезом. После этого по всей стране в период с 1 апреля 2016 года по 31 марта 2017 года была проведена оценка охвата регулярным скрининговым обследованием детей младше пяти лет, находившихся в контакте с инфицированным человеком, на предмет выявления активного туберкулеза и соответствующей доли таких детей, для которых при необходимости была назначена профилактическая терапия. В 2016 году мы оценили показатели латентной туберкулезной инфекции в области Верхних Бассейнов до и после того, как работники здравоохранения начали активное отслеживание детей младше пяти лет, находившихся в контакте с инфицированным человеком.В Буркина-Фасо в течение периода исследования авторов в результате регулярного скрининга и пассивного отслеживания контактов было зарегистрировано 3717 случаев туберкулеза легких и 1166 соответствующих детей младше пяти лет, находившихся в контакте с инфицированным человеком. Общее соотношение «контакт/показатель» составило 0,31, соответствующий охват скрининговым обследованием — 82,0% (956/1166), а доля детей, для которых было назначено профилактическое лечение, — 90,5% (852/941). Активное отслеживание в области Верхних Бассейнов привело к значительно более высокому соотношению «контакт/показатель» (1,83) и охвату скрининговым обследованием (99,3%, 145/146).Недавно созданная система регистрации и отчетности оказалась выполнимой и удобной для пользователей и позволила измерить глобальные показатели латентной туберкулезной инфекции. При сравнении с активным отслеживанием пассивное отслеживание привело к значительно более низким показателям количества детей, находившихся в контакте с инфицированным человеком.

Xpert MTB/Rif should be used as an alternative test for microscopy for TB diagnosis in low incidence settings http://ow.ly/JQCF30i8nO3

As tuberculosis (TB) spreads beyond borders with people movements, several interventions ensuring the continuity of care are essential, although difficult to put in place in the absence of well-defined agreements allowing data sharing and easy referral of patients to appropriate health facilities. This article first sets out general principles for cross-border collaboration and continuity of care. It then presents a series of case studies. Policies and practices on cross-border collaboration in selected low-incidence countries (Australia, Italy, Norway, The Netherlands, the United Kingdom and the United States) are described and critically appraised. Details of the World Health Organization's (WHO's) European Respiratory Society TB Consilium for transborder migration and those of the Health Network's TBNet activities are described. With increasing population movement, including migrants and travellers, it is time to build on good practices and existing tools and to remove legal, financial and social barriers to ensure early diagnosis, full treatment and continuity of care across our world. Data sharing between the sending and the receiving countries is of utmost importance and must be conducted in line with privacy protection rules. Successful implementation of these interventions is key to being on track with the WHO's End TB strategy targets for 2030.

Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. The World Health Organization (WHO) has implemented and scaled-up three important global public health strategies (i.e., DOTS, Stop TB, and End TB) to improve the international scenario. Their epidemiological impact was relevant, as they decreased the number of potential new cases of disease and death. However, the emergence and spread of TB/HIV coinfection and multidrug-resistant TB have hindered the progress towards the elimination of TB by 2050. More efforts are required to increase the global annual decline of the TB incidence rate. Political commitment is necessary, with global and national strategies oriented to the adoption and adaptation of the international, evidence-based recommendations on diagnosis, treatment, and prevention. Research and development activities should be planned to improve the current tools adopted to fight the disease. New rapid diagnostics, an updated and effective therapeutic armamentarium, and an effective preventive vaccine could represent the solution to address the current epidemiological threats.

BACKGROUND Tuberculosis (TB) is the major cause of mortality in HIV-infected children globally. Current guidelines about the management of antiretroviral therapy in children with TB are based on a limited number of nonrandomized studies involving small numbers of participants. The aim of the study was to systematically retrieve and critically appraise available evidence on the efficacy and safety of different antiretroviral regimens in children with HIV infection who are receiving treatment for active TB. METHODS We conducted a systematic review of the literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Records were retrieved through March 2016 from Medline, Embase and manual screening of key conference proceedings. Four specific research questions assessing available treatment options were defined. RESULTS Although 4 independent searches were conducted (1 for each Population, Intervention, Comparator, Outcomes question), results were elaborated and interpreted together because of significant overlap among the retrieved records. Six observational studies were selected for qualitative synthesis while meta-analysis could not be performed. CONCLUSION Evidence for optimal treatment options for HIV/TB coinfected children is limited. As the global community strives to reach the fast-track HIV treatment targets and eliminate childhood TB deaths, it must ensure that coinfected children are included in key treatment studies and expand this neglected but crucial area of research.

The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed. Also, special topics on drug interactions, TB-IRIS and TB relapse are also described. Notwithstanding the defeats and meagre investments, diagnosis and management of the two diseases have seen significant and unexpected improvements of late. On the HIV side, expansion of ART coverage, development of new updated guidelines aimed at the universal treatment of those infected, and the increasing availability of newer, more efficacious and less toxic drugs are an essential element to controlling the two epidemics. On the TB side, diagnosis of MDR-TB is becoming easier and faster thanks to the new PCR-based technologies, new anti-TB drugs active against both sensitive and resistant strains (i.e. bedaquiline and delamanid) have been developed and a few more are in the pipeline, new regimens (cheaper, shorter and/or more effective) have been introduced (such as the "Bangladesh regimen") or are being tested for MDR-TB and drug-sensitive-TB. However, still more resources will be required to implement an integrated approach, install new diagnostic tests, and develop simpler and shorter treatment regimens.

Background: Carbapenems are used to treat MDR/XDR-TB cases in order to build a robust regimen, however limited evidence of their effectiveness exists. Aim: To compare the therapeutic contribution of imipenem and amoxicillin/clavulanate (IC) vs. meropenem and amoxicillin/clavulanate (MC) added to background regimens to treat MDR/XDR-TB cases. Methods: An observational, retrospective, cohort study was performed in 5 centres in Europe and South America, consecutive adult patients with bacteriologically proven MDR-TB were recruited and divided by MC and IC exposure. Demographic, epidemiological, microbiological, and clinical variables were collected using standardized e-forms. Results: A cohort of 180 MDR-TB patients were enrolled: 84 and 96 were treated with IC and MC respectively. Both groups had similar median number of antibiotic resistances (8 vs. 8) but more fluoroquinolone resistance (79.0% vs. 48.9% ; p-value: Conclusion: Our study suggests that MC is safe and more effective than IC in treating M/XDR-TB patients.

Tuberculosis (TB) is a major public health issue worldwide, with ~9.6 million new incident cases and 1.5 million deaths in 2014. The End-TB Strategy launched by the World Health Organization in the context of the post-2015 agenda aims to markedly abate the scourge of TB towards global elimination, by improving current diagnostic and therapeutic practices, promoting preventative interventions, stimulating government commitment and increased financing, and intensifying research and innovation. The emergence and spread of multidrug-resistant strains is currently among the greatest concerns, which may hinder the achievement of future goals. It is crucial that primary healthcare providers are sufficiently familiar with the basic principles of TB diagnosis and care, to ensure early case detection and prompt referral to specialised centres for treatment initiation and follow-up. Given their special relationship with patients, they are in the best position to promote educational interventions and identify at-risk individuals as well as to improve adherence to treatment.

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, pversus 5 (4–6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49–156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.

Simon Tiberi, Giovanni Sotgiu, Lia D’Ambrosio, Rosella Centis, Marcos Abdo Arbex, Edith Alarcon Arrascue, Jan Willem Alffenaar, Jose A. Caminero, Mina Gaga, Gina Gualano, Alena Skrahina, Ivan Solovic, Giorgia Sulis, Marina Tadolini, Valentina Alarcon Guizado, Saverio De Lorenzo, Aurora Jazmin Roby Arias, Anna Scardigli, Onno W. Akkerman, Alena Aleksa, Janina Artsukevich, Vera Avchinko, Eduardo Henrique Bonini, Felix Antonio Chong Marin, Lorena Collahuazo Lopez, Gerard de Vries, Simone Dore, Heinke Kunst, Alberto Matteelli, Charalampos Moschos, Fabrizio Palmieri, Apostolos Papavasileiou, Marie-Christine Payen, Andrea Piana, Antonio Spanevello, Dante Vargas Vasquez, Pietro Viggiani, Veronica White, Alimuddin Zumla and Giovanni Battista Migliori

Evaluation of drug resistances is needed to identify candidates for the shorter regimen in MDR-TB hot spots http://ow.ly/wZV33022VXt

Translating the potential of Xpert(®) MTB/RIF into more effective tuberculosis (TB) care and control in low-income settings is challenged by operational issues. We report the experience in introducing this technology in Burkina Faso through a centralised approach. Xpert was successfully integrated into the diagnostic algorithm of multidrug-resistant TB cases. However, barriers to Xpert use for the diagnosis of TB in vulnerable populations, such as persons living with human immunodeficiency virus infection and children, were observed, mainly due to lack of coordination between services. Lessons learnt can be exploited to optimise the roll-out of this technology at country level.

Rickettsia felis is an emerging spotted fever group pathogen that may be responsible for potentially life-threatening infections. A cosmopolitan distribution has been postulated though most human cases were observed in Africa and the Americas. We report an imported case from Nepal that occurred in an Italian tourist who presented with a 1-week history of fever, headache, nausea, vomiting, and a mild maculopapular rash 14 days after return.

Background This study aimed to assess the pharmacokinetic profile of rifabutin (RBT) given at 150 mg or 300 mg every other day (EOD) in tuberculosis (TB)-HIV co-infected adult patients. Methods This is a pharmacokinetic prospective, pilot, open, randomised study of two doses of RBT in combination with lopinavir/ritonavir among HIV−TB patients in Burkina. Sixteen patients were randomised in two arms: TB treatment consisting HZE standard doses in association with RBT150 mg EOD (arm A, 8 patients) or RBT300 mg EOD (arm B, 8 patients) in combination with lopinavir/ritonavir. RBT plasma concentrations were evaluated after two weeks of combined HIV and TB treatment. Samples were collected at pre-dosing and at 1, 2, 3, 4, 6, 8 and12 hours after drug ingestion to measure plasma drug concentration using HPLC–MS/MS assay. Results The mean Cmax and AUC in the RBT 150 mg arm (Cmax=0.35±0,18 µg/mL, AUC(0–24)=3.94±2,1 µg.h/mL) were significantly lower (p=0.01) than those of the RBT 300 mg arm (Cmax=0.75±0.54 µg/mL AUC(0–24)=7.1±2.7 µg.h/mL). There was no significant difference in Tmax (Tmax=3.44±2.01 hours vs Tmax=3.86±2.04 hours) p=0.687. RBT follows linear kinetics and no significant differences were apparent in the mean oral clearance (CL/F) estimates (p=0.683), which were dose independent and similar for the 2 assessment doses. Five of 8 patients in RBT150 mg arm had a Cmax below plasma therapeutic limit ( 0.06 µg/mL) compared with 4 of 8 patients in the RBT150 mg arm. The means Cmax, AUC (0–24) and Tmax of 25-O-desacetyl rifabutin of the RBT 300 mg arm were increased by 100% and 50% respectively compared to the RBT150 mg arm. Conclusions This study confirmed that the dose of rifabutin 150 mg three times a week in combination with lopinavir/ ritonavir is inadequate and could lead to the selection of rifamycin-resistant mycobacteria.

Whipple's disease is a rare systemic condition resulting from a chronic infection by Tropheryma whipplei. Clinical presentation can be widely heterogeneous, often leading to delayed diagnosis and treatment. Furthermore, little is known about the underlying pathogenic mechanisms, although several abnormalities in immune cell function have been observed. We describe the case of a 51-year-old woman presenting with dysphagia, odynophagia, long-lasting low-grade fever, and malabsorption syndrome who underwent an upper gastrointestinal endoscopy showing esophageal candidiasis. On the same occasion, duodenal biopsies were also performed, with evidence of mucosal infiltration of periodic acid-Schiff-positive and CD68+ foamy macrophages at microscopic examination. Such findings were suggestive of Whipple's disease, as also confirmed by molecular analysis by PCR for T. whipplei. No specific risk factors were identified in our patient that could explain the occurrence of an opportunistic infection such as candida esophagitis, thus leading to the hypothesis of a direct correlation with Whipple's disease. Interestingly, a Giardia lamblia coinfection was subsequently identified, which is consistent with an underlying immune deficit although still undefined.

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.

Background Sexually transmitted infections are widespread globally, especially among people aged 15–25. Chlamydia trachomatis is the most common sexually-acquired bacterial disease. This infection is not notified in Italy; prevalence data on population-based surveys are not available. Methods We conducted a prevalence survey among students aged 18 or older attending high schools in the Province of Brescia, Northern Italy. A total of 3134 adolescents were offered to enter the study; overall, 1886/3134 (60.2%) participated. Each consenting student answered to a socio-behavioural questionnaire and C. trachomatis and N. gonorrhoeae were searched on first void urine samples using VERSANT ® CT/GC DNA 1.0 Assay (kPCR). We present preliminary data concerning 1311 enrolled individuals attending 16 schools. Results Overall, 63.8% (836/1311) were females and the median age was 18.4 years. Most students (91.7%) were born in Italy. 77.1% of the enrolled students declared to be sexually active (F > M, p F, p = 0.017) admitted always using it. Females were found to become sexually active earlier, had more partners in the previous six months and less frequently used condoms. No case of N. gonorrhoeae infection was identified, while 8 males and 13 females were positive for C. trachomatis, with a prevalence rate among sexually active students of 2.4% (IC 95%:1.0–4.8) and 1.9% (IC 95%:1.0–3.3) respectively. The factors significantly associated with an increased risk of Chlamydial infection were the inconsistent condom use (p = 0.029) and a higher number of sexual partners during the previous six months (p = 0.013). Conclusion A lower than expected prevalence of C. trachomatis infection was observed among sexually active adolescents in Northern Italy. Study conducted with scientific and logistic support from Copan S.p.A. and Siemens Healthcare Diagnostic S.p.A.

Background Aim of our study is to investigate the clinical and immunological outcomes according to first-line HAART adherence in a large cohort of HIV-infected patients in Burkina Faso. Methods A retrospective study was conducted between 2001 and 2009 among patients from two urban medical centers [St. Camille Medical Center (CMSC) and “Pietro Annigoni” Biomolecular Research Center (CERBA)] and 1 in the rural District of Nanoro (St. Camille District Hospital). Socio-demographical and clinical data were analyzed. Adherence was evaluated through a questionnaire investigating 5 key points related to drugs, consultations and blood exams, by assigning 0 to 2 points each up to 10 points overall. Data were collected at baseline and regularly thereafter. Adherence score was considered as a continuous variable and classified in optimal (8–10 points) and sub-optimal (0–7 points). Immunological outcome was evaluated as modification in CD4+ T-cell count over time, while predictors of death were explored by a univariate and multivariate Cox model considering adherence score as a time-varying covariate. Results A total of 625 patients were included: 455 (72.8%) were females, the median age was 33.3 (IQR 10.2) years, 204 (32.6.%) were illiterates, the median CD4+ T-cell count was 149 (IQR 114) cells/μl at baseline. At the end of the observation period we recorded 60/625 deaths and 40 lost to follow-up. The analysis of immunological outcomes showed a significant variation in CD4+ T-cell count between M12 and M24 only for patients with optimal adherence (Δ=78.2, p

Tuberculosis (TB) is a leading cause of death among women of childbearing age, and may be responsible for severe complications during pregnancy. Between August 2014 and March 2015, we conducted a pilot project to promote active TB case finding in antenatal care (ANC) clinics in the Central Region of Burkina Faso. Our results show very limited TB diagnostic practices and possible severe underdiagnosis of TB at ANC clinics, despite adequate screening practices. Integration of training and supervision of TB diagnosis and treatment into ANC services is required.