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This study aims to assess antimicrobial consumption in the pediatric department of a tertiary care public hospital in Zimbabwe. Clinical records of pediatric inpatients admitted to Harare Central Hospital over a 3-week period were reviewed prospectively. Antimicrobial consumption was described as days of therapy per 100 inpatient days (DOT/100 PD). Adherence of antimicrobial drug prescriptions to the National Guidelines was also evaluated. A total of 121 (93.1%) children were prescribed at least one antimicrobial out of 130 children admitted. The median age was 14 months (IQR: 3 – 48 months). Overall antimicrobial consumption was 155.4 DOT / 100 PD (95% CI 146-165.2). The most frequently prescribed antimicrobials were benzylpenicillin, gentamicin and ceftriaxone. Prescriptions were adherent to national guidelines in 57.7% of children. This study shows that there is high antimicrobial drug usage in hospitalized children in Zimbabwe and a considerable proportion of prescriptions are non-adherent with national guidelines.

Background: The primary goal was to estimate the seroprevalence of autochthonous hepatitis E virus (HEV) infection in adult Romanian population. Additionally, we aimed to identify the risk factors associated with the HEV seropositive status. Methods: Between January 2015 and December 2016, 201 adult patients were tested for antiHEV-IgG. Multivariate logistic regression was used to examine for factors associated with a positive HEV-IgG test. The level of significance was set at α = 0.05. Results: The final analysis included 175 patients who followed the study protocol. Forty-sex (26.3%) had positive, 121 (69.1%) had negative, and 8 (4.6%) had indeterminate antiHEV-IgG results. Patients with positive anti-HEV-IgG were older [median age: 54.5 years (IQR 43-65)] compared to patients with negative anti-HEV-IgG [median age: 37.5 years (IQR 28-57.5)], p Conclusions: In conclusion, we found that autochthonous HEV seropositivity is common in our study population, especially in older patients, previous blood transfusions, presence of immunosuppressive conditions, and positive HBsAg.

Background: Treatment for urinary tract infections (UTIs) is usually empiric and is based on local antimicrobial resistance data. These data, however, are scarce in low-resource settings. The aim of this study is to determine the impact of antibiotic treatment on clinical and bacteriological outcomes in patients presenting with UTI symptoms to primary care in Harare. Methods: This cohort study enrolled participants presenting with UTI symptoms to 10 primary healthcare clinics in Harare between July 2019 and July 2020. A questionnaire was administered and a urine sample was collected for culture. If the urine culture showed growth of ≥105 colony forming units/mL of a uropathogen, a follow up visit at 7-21 days was conducted. Results: The analysis included 168 participants with a median age of 33.6 years (IQR 25.1-51.4) and of whom 131/168 (78.0%) were female. Effective treatment was taken by 54/168 (32.1%) participants. The urine culture was negative at follow up in 41/54 (75.9%) of participants who took appropriate treatment and in 33/114 (28.9%, p Conclusion: The findings of this study show that effective treatment leads to symptom resolution and bacterial clearance in people presenting with UTIs to primary care. Although UTIs are not life-threatening and can resolve without treatment, they do impact on quality of life, highlighting the need for optimised treatment recommendations.

Background People living with HIV may be at increased risk for infections with resistant organisms. Infections with ESBL-producing organisms are of particular concern because they limit treatment options for severe Gram-negative infections in low-resource settings. Objectives To investigate the association between HIV status and urinary tract infections (UTIs) with ESBL-producing Escherichia coli. Patients and methods Cross-sectional study enrolling adults presenting with UTI symptoms to primary care clinics in Harare, Zimbabwe. Demographic and clinical data were collected during interviews and a urine sample was collected for culture from each participant. Antimicrobial susceptibility testing was performed according to EUCAST recommendations. Results Of the 1164 who were enrolled into the study, 783 (64%) were female and 387 (33%) were HIV infected. The median age was 35.8 years. Urine cultures were positive in 338 (29.0%) participants, and the majority of bacterial isolates were E. coli (n = 254, 75.2%). The presence of ESBL was confirmed in 49/254 (19.3%) E. coli. Participants with HIV had a 2.13 (95% CI 1.05–4.32) higher odds of infection with ESBL-producing E. coli than individuals without HIV. Also, the prevalence of resistance to most antimicrobials was higher among participants with HIV. Conclusions This study found an association between HIV and ESBL-producing E. coli in patients presenting with symptoms suggestive of UTI to primary care in Harare. HIV status should be considered when prescribing empirical antimicrobial treatment.

Before the coronavirus 2019 (COVID-19) pandemic began, antimicrobial resistance (AMR) was among the top priorities for global public health. Already a complex challenge, AMR now needs to be addressed in a changing healthcare landscape. Here, we analyse how changes due to COVID-19 in terms of antimicrobial usage, infection prevention, and health systems affect the emergence, transmission, and burden of AMR. Increased hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR pathogen selection and spread in the short term. However, the opposite effects may be seen if antibiotics are more widely used as standard healthcare pathways break down. Over 6 months into the COVID-19 pandemic, the dynamics of AMR remain uncertain. We call for the AMR community to keep a global perspective while designing finely tuned surveillance and research to continue to improve our preparedness and response to these intersecting public health challenges.

Antimicrobial resistance surveillance data is lacking from many resource-limited settings mainly due to limited laboratory testing. Novel culture systems may address some of the limitations of conventional culture media and expand the availability of microbiology services. The aims of this study were to evaluate the performance of InTray COLOREX Screen/ESBL and Compact Dry for the detection of uropathogens and of extended-spectrum beta-lactamase (ESBL)-producing organisms from urine samples. Urines samples were collected from patients presenting with symptoms of urinary tract infection to primary care clinics in Harare. Performance of the InTray COLOREX Screen, ESBL and Compact Dry chromogenic media were compared to the reference of culture using Brilliance UTI agar and conventional antimicrobial susceptibility testing. A total of 414 samples were included in the analysis. Of the included samples, 98 were positive on Brilliance UTI agar and 83 grew Enterobacterales. The sensitivities and specificities for Enterobacterales were 89.2% (95% CI 80.4–94.9) and 98.2% (95% CI 96.1–99.3) for InTray Screen and 95.2% (95% CI 88.1–98.7) and 99.7% (95% CI 98.3–100) for Compact Dry. Extended-spectrum beta-lactamases were present in 22 isolates from the Brilliance UTI agar. The sensitivity of the InTray COLOREX ESBL culture plates for the detection of ESBL-producing organisms was 95.5% (95% CI 77.2–99.9) and specificity was 99.5% (95% CI 98.2–99.9%). Our findings show good performance of the novel culture systems for the detection of uropathogens and ESBL-producing organisms. Both systems have several advantages over conventional media and have the potential to expand and decentralize laboratory testing. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04312-4.

Background: Increasing antimicrobial resistance (AMR) is threatening our ability to effectively treat infections. People living with HIV (PLWH) may be at increased risk of infections with resistant organisms due to more frequent healthcare utilisation and antimicrobial prescriptions. This systematic review investigated the association between HIV and AMR. Methods: Studies reporting on AMR for colonisation or infection with bacterial pathogens excluding mycobacteria and bacteria causing sexual transmitted infections stratified by HIV status, species and antimicrobial tested were included. Pooled odds ratios were used to evaluate the association between HIV and resistance. The completeness of reporting was evaluated using the STROBE checklist. Findings: A total of 92 studies from 23 countries published between 1995 and 2020 were identified. The studies included the following organisms: Staphylococcus (n=47), Streptococcus pneumoniae (n=28), Escherichia coli (n=6) and other Gram-negative bacteria. PLWH had a 2·12 (95% CI 1·36-3·30) higher odds for colonization and 1·90 (95%CI 1·45-2·48) higher odds for infection with methicillin-resistant S. aureus; a 2·28 (95%CI 1·75-2·97) higher odds of infections with S. pneumoniae with decreased penicillin susceptibility and a 1·59 (95%CI 0·83-3·05) higher odds of resistance to third-generation cephalosporins in E. coli and Klebsiella pneumoniae. Overall, there was a high heterogeneity between studies. Interpretation: This review shows an increased risk of AMR in PLWH across a range of bacterial pathogens and multiple drug classes, which has important clinical implications for treatment. The lack of laboratory capacity for identifying AMR and limited access to alternative treatment options in countries with the highest burden of HIV highlights the need for more research on AMR in PLWH. This knowledge should translate into treatment guideline changes especially in settings where diagnostics are limited. Funding: IDO received funding though the Wellcome Trust Clinical PhD Programme awarded to the London School of Hygiene & Tropical Medicine (grant number 203905/Z/16/Z). Declaration of Interests: None of the authors have any competing interests.

Summary Background The prevalence of sexually transmitted infections (STIs) among youth is high in sub-Saharan Africa. We investigated the uptake of testing for and prevalence of Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhoea) infections among youth in community-based settings in Zimbabwe, and explored the facilitators and barriers to testing. Methods This study was nested within a cluster randomised trial of community-based delivery of integrated HIV and sexual and reproductive health services for youth aged 16–24 years. Chlamydia and gonorrhoea testing via urine samples using the Xpert CT/NG test was offered in the four intervention clusters in Harare, Zimbabwe. Factors associated with testing uptake were investigated in a subset of participants (n=257) using hierarchical multivariate logistic regression. In-depth interviews with a separate purposively selected sample (n=26) explored facilitators and barriers to STI testing and partner notification and were analysed using thematic analysis. Findings Between June 1, 2019, and Jan 31, 2020, there were 6200 attendances by 4440 participants (78·2% women, 21·8% men) median age 20·3 (IQR 17·9–22·8) years. 1478 participants had 1501 tests done, and 248 tests were positive and 1253 tests were negative for chlamydia or gonorrhoea, or both. STI test uptake was 33·3% (95% CI 31·9–34·7), increasing from 11·7% in June, 2019, to 37·1% in January, 2020. The prevalence of chlamydia or gonorrhoea, or both, was 16·5% (95% CI 14·7–18·5; 248 of 1501), with only seven participants (3%) showing symptoms. The overall yield of testing was 4·0% (95% CI 3·5–4·5; 248 of 6200). Uptake was associated with having symptoms (adjusted odds ratio [OR] 14·8, 95% CI 1·66–132·07) and negatively associated with being single (adjusted OR 0·33, 95% CI 0·13–0·84) or having a boyfriend or girlfriend (adjusted OR 0·19, 95% CI 0·087–0·43) compared with being married, and being a student compared with being employed (adjusted OR 0·26, 95% CI 0·10–0·68). Perceived risk and symptoms of STIs were motivators for testing whereas misinformation, anticipated stigma, and concern about confidentiality were barriers. Interpretation The prevalence of chlamydia or gonorrhoea, or both, was high among youth but only a minority were symptomatic. Therefore most infections would remain untreated without access to STI testing. Provision of education, counselling, and confidentiality are essential to improve uptake and acceptability of STI testing. Funding Wellcome Trust.

Antimicrobial resistance (AMR) is compromising our ability to successfully treat infections. There are few data on gram-negative AMR prevalence in sub-Saharan Africa especially from the outpatient setting. This study aims to investigate the prevalence of and underlying molecular mechanisms for AMR in gram-negative bacilli causing urinary tract infections (UTIs) in Zimbabwe. Risk factors for AMR and how AMR impacts on clinical outcomes will also be investigated.Adults presenting with UTI symptoms at primary health clinics in Harare will be included. A questionnaire will be administered, and urine samples will be collected for culture. Participants with positive urine cultures will be followed up at 7-14 days post-enrolment. All participants will also be followed by telephone at 28 days to determine clinical outcomes.Bacterial identification and antibiotic susceptibility testing will be performed on positive cultures.The results from this study will be used to inform policy and development of treatment recommendations. Whole genome sequencing results will provide a better understanding of the prevalent resistance genes in Zimbabwe, of the spread of successful clones, and potentially will contribute to developing strategies to tackle AMR.

Young people living with HIV (YPLHIV) in sub-Saharan Africa (SSA) are at high risk of having a poor quality of life. Addressing wellbeing explicitly within HIV/AIDS policies could assist mitigation efforts. However, guidance on wellbeing measures to evaluate policies for YPLHIV is scarce. The aims of this mixed-methods review were to identify: i) key dimensions of wellbeing and ii) wellbeing measures that align to these dimensions among YPLHIV (15–24 years) in SSA. We searched six social science and medical databases, including grey literature. We included studies that examined correlates and lived experiences of wellbeing, among YPLHIV in SSA, from January 2000 to May 2019. Two reviewers independently screened abstracts and full texts and assessed methodological quality of included articles. We analysed quantitative and qualitative data using descriptive and meta-ethnographic approaches, respectively. Thereafter, we integrated findings using a framework approach. We identified 6527 citations. Of these, 10 quantitative and 30 qualitative studies were included. Being male, higher educational status, less stigma and more social support were likely correlates of wellbeing. Themes that shaped experiences suggestive of wellbeing were: 1) acceptance and belonging— stigma, social support; 2) coping; 3) standard of living. Our final synthesis found that the following dimensions potentially characterise wellbeing: self-acceptance, belonging, autonomy; positive relations, environmental mastery, purpose in life. Wellbeing for YPLHIV is multi-dimensional and relational. Relevant measures include the Personal Wellbeing Index, Ryff’s Psychological Wellbeing Scale and Mental Health Continuum Short Form. However, psychometric evaluations of these scales among YPLHIV in SSA are needed.

Introduction: There are positive aspects regarding the prescribing of fixed-dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower and middle income countries (LMICs) which have the greatest prevalence of both infectious and non-infectious diseases and issues of affordability. Areas covered: Review of potential advantages, disadvantages, cost-effectiveness and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where concerns with their value. Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis and hypertension are valued and listed in country’s essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which is being addressed.

National Mycobacterium Reference Laboratory, Borstel, Germany. : To evaluate the effectiveness of OMNIgene®•SPUTUM (OM-S) reagent in comparison with a method using N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) with regard to mycobacterial recovery and contamination of broth and solid cultures. : Sputum samples from patients with tuberculosis and other respiratory diseases underwent decontamination with NALC-NaOH-based (MycoDDR™) or OM-S reagent. The decontamination procedure was assigned by block randomisation. Samples were inoculated on Lowenstein-Jensen, Stonebrink and MGIT™ (Mycobacterial Growth Indicator Tubes). Mycobacterial recovery from samples spiked with Mycobacterium tuberculosis following decontamination was determined. : Eighty-five samples were randomised to NALC-NaOH and 84 to OM-S reagent. Mycobacterial recovery was significantly lower for samples processed with OM-S reagent compared with the NALC-NaOH method across all media types. Culture contamination was lower with NALC-NaOH reagent on solid media (9.4-12.9% vs. 28.6-29.8%). Growth was not observed in MGIT among samples spiked with 10 600-16 800 colony-forming units of M. tuberculosis following decontamination with OM-S reagent. : Low mycobacterial recovery, especially in MGIT, observed in the present study suggests that OM-S reagent might not be compatible with the MGIT system. More extensive field evaluations of the OM-S reagent are warranted to demonstrate a significant benefit over currently used methods.

Background The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. Objective Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. Our approach Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. Ongoing activities Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. Conclusion There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

Günther Fink and colleagues are to be congratulated for their analysis of antibiotic exposure among children younger than 5 years in low-income and middle-income countries (LMICs) with a range of common illnesses, including cough, fever, diarrhoea, and malaria.1 The authors explain that their study1 is the first to use a robust method to comprehensively quantify cumulative antibiotic exposure among children in LMICs by obtaining nationally representative data from surveys of households and formal-sector health-care facilities. Quantifying exposure is important, as previous surveys have only had limited coverage in low-income settings, particularly in sub-Saharan African countries, which have the highest incidence of infectious diseases globally.2,3 However, quantifying true antibiotic use in LMICs might be difficult if antibiotics are frequently purchased without a prescription due to issues with affordability and access. Obtaining antibiotics in this way accounts for up to 93% of all antibiotics dispensed in some LMICs.4,5 The remaining 7% or more include antibiotics obtained from ambulatory care and inpatient hospital care.2 Antimicrobial resistance is a growing public

Background Overuse of antibiotics is one of the main drivers for antimicrobial resistance (AMR). Globally, most antibiotics are prescribed in the outpatient setting. This survey aimed to explore attitudes and practices with regards to microbiology tests, AMR and antibiotic prescribing among healthcare providers at public primary health clinics in Harare, Zimbabwe. Methods This cross-sectional survey was conducted in nine primary health clinics located in low-income suburbs of Harare between October and December 2020. In Zimbabwe, primary health clinics provide nurse-led outpatient care for acute and chronic illnesses. Healthcare providers who independently prescribe antibiotics and order diagnostic tests were invited to participate. The survey used self-administered questionnaires. A five-point Likert scale was used to determined attitudes and beliefs. Results A total of 91 healthcare providers agreed to participate in the survey. The majority of participants (62/91, 68%) had more than 10 years of work experience. Most participants reported that they consider AMR as a global (75/91, 82%) and/or national (81/91, 89%) problem, while 52/91 (57%) considered AMR to be a problem in their healthcare facilities. A fifth of participants (20/91, 22%) were unsure if AMR was a problem in their clinics. Participants felt that availability of national guidelines (89/89, 100%), training sessions on antibiotic prescribing (89/89, 100%) and regular audit and feedback on prescribing (82/88, 93%) were helpful interventions to improve prescribing. Conclusions These findings support the need for increased availability of data on AMR and antibiotic use in primary care. Educational interventions, regular audit and feedback, and access to practice guidelines may be useful to limit overuse of antibiotics.

Objective: The aim of our study was to retrospectively validate a previously described rapid clinical score (RCS) in distinguishing tuberculous meningitis (TBM) from viral meningitis (VM) in people who are at increased risk of tuberculosis, as well as from cryptococcal meningitis (CM) in HIV-infected patients. Methods: We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases. The variables included in RCS were duration of symptoms before admission, neurological stage, cerebrospinal fluid (CSF) to blood glucose ratio, and CSF protein. We included in this retrospective study 31 patients with definite or probable TBM including 14 HIV-infected patients, 62 HIV-noninfected patients with VM, and 18 HIV-infected patients with CM. Results: The sensitivity of RCS to distinguish TBM from VM was 96.7%, with a specificity of 81.1% and the area under the receiver operating characteristic (ROC) curve was 0.949 (0.90–0.99). When all four criteria from the RCS were present, the specificity increased at 100%. In HIV-infected patients, the sensitivity and specificity of RCS in differentiating TBM from CM were 86.6% and 27.7%, respectively, and the area under the ROC curve was 0.669 (0.48–0.85). Conclusion: This easy-to-use RCS was found to be helpful in differentiating TBM from VM, with a better sensitivity than molecular amplification techniques and a relatively good specificity. However, the RCS was not useful to differentiate between TBM and CM in HIV-infected patients.

RATIONALE: We evaluated whether treatment outcomes for patients with multidrug-resistant and extensively drug-resistant tuberculosis can be substantially improved when sufficient resources for personalizing medical care are available. OBJECTIVES: To describe the characteristics and outcomes of patients with pulmonary multidrug-resistant tuberculosis at the Otto Wagner Hospital in Vienna, Austria. METHODS: We conducted a retrospective single-center study of patients initiated on treatment for multi-drug resistant tuberculosis between January 2003 and December 2012 at the Otto Wagner Hospital, Vienna, Austria. The records of patients with multidrug-resistant tuberculosis were reviewed for epidemiological, clinical, laboratory, treatment, and outcome data. MEASUREMENTS AND MAIN RESULTS: Ninety patients with pulmonary multidrug-resistant tuberculosis were identified. The median age was 30 years (interquartile range, 26-37). All patients were of non-Austrian origin, and 70 (78%) came from former states of the Soviet Union. Thirty-nine (43%) patients had multidrug-resistant tuberculosis; 28 (31%) had additional bacillary resistance to at least one second-line injectable drug and 9 (10%) to a fluoroquinolone. Fourteen (16%) patients had extensively drug-resistant tuberculosis. Eighty-eight different drug combinations were used for the treatment of the 90 patients. Surgery was performed on 10 (11.1%) of the patients. Sixty-five (72.2%) patients had a successful treatment outcome, 8 (8.9%) defaulted, 3 (3.3%) died, 8 (8.9%) continued treatment in another country and their outcome was unknown, and 6 (6.7%) were still on therapy. None of the patients experienced treatment failure. Treatment outcomes for patients with extensively drug-resistant tuberculosis were similar to those of patients with multidrug-resistant tuberculosis. CONCLUSIONS: High rates of treatment success can be achieved in patients with multidrug-resistant and extensively drug-resistant tuberculosis when individually tailored treatment regimens can be provided in a high-resource setting.

We would like to thank Dr. Navisha Dookie and colleagues for their comment and for sharing their view on genotypic drug-susceptibility testing (DST) to predict phenotypic drug-susceptibility for the management of patients with drug-resistant tuberculosis (1, 2). We agree that DST should ideally be conducted for all drugs in a regimen, particularly given the severe adverse effects of second-line anti-tuberculosis drugs. Yet, even whole-genome sequencing in not a one-size-fits-all solution. Instead, the goal has to be to optimally combine genotypic and phenotypic assays in a diagnostic algorithm that capitalises on the strengths of both approaches whilst including appropriate reflex and confirmatory testing to minimize the impact of their respective limitations, including systematic errors (3).

BACKGROUND: Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. OBJECTIVE: To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. METHOD: Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany. Treatment was conducted following current guidelines and individualised on the basis of drug susceptibility testing. Two-month and 6-month sputum smear and sputum culture conversion rates were assessed. A clinical and radiological score were used to assess response to anti-tuberculosis treatment. RESULTS: Non-M/XDR-TB (n = 29) and M/XDR-TB (n = 46) patients showed similar rates of microbiological conversion: 2-month smear conversion rate, 90% vs. 78%; culture conversion rate, 67% vs. 61%; time to smear conversion, 19 days (IQR 10-32) vs. 31 days (IQR 14-56) (P = 0.066); time to culture conversion, 39 days (IQR 17-67) vs. 39 days (IQR 6-85) (P = 0.191). Both clinical and radiological scores decreased after the introduction of anti-tuberculosis treatment. CONCLUSION: There were no significant differences in scores between the two groups until 6 months of treatment. Under optimal clinical conditions, with the availability of novel diagnostics and a wide range of therapeutic options for individualised treatment, patients with M/XDR-TB achieved 6-month culture conversion rates that were compatible with those in patients with non-M/XDR-TB.

Multidrug-resistant (MDR) tuberculosis (TB), defined by bacillary resistance against rifampicin and isoniazid, has been identified as a global threat to mankind [1]. According to the latest report by the European Centres for Disease Prevention and Control, and World Health Organization (WHO) regional office for Europe, only approximately 50% of MDR-TB patients in Europe reach favourable treatment outcomes [2]. Successful treatment outcomes are achieved for less than 25% of patients with extensively drug-resistant (XDR)-TB (MDR plus resistance against a least one fluoroquinolone and one second-line injectable drug) in the European Union/European Economic Area Countries [2].

The emergence of MDR-TB is a cause of great concern due to difficulties in patient management and poor treatment outcomes. Currently the duration of treatment and the choice of drugs for patients with MDR-TB are standardized in many countries. This might not be the best approach since the optimal therapy may depend on different pathogen- and host-related features. Combining the introduction of technological innovations such as whole bacillary genome sequencing for the identification of drug-resistance-associated mutations, therapeutic drug monitoring and host-directed therapies with an individualized approach to MDR-TB management will likely lead to more tolerable, shorter and more efficient treatment regimens and an increase in the quality of life of those affected by MDR-TB.

More than 2 million people fleeing conflict, persecution, and poverty applied for asylum between 2015 and 2016 in the European Union. Due to this, medical practitioners in recipient countries may be facing a broader spectrum of conditions and unusual presentations not previously encountered, including a wide range of infections with pulmonary involvement. Tuberculosis is known to be more common in migrants and has been covered broadly in other publications. The scope of this review was to provide an overview of exotic infections with pulmonary involvement that could be encountered in refugees and migrants and to briefly describe their epidemiology, diagnosis, and management. As refugees and migrants travel from numerous countries and continents, it is important to be aware of the various organisms that might cause disease according to the country of origin. Some of these diseases are very rare and geographically restricted to certain regions, while others have a more cosmopolitan distribution. Also, the spectrum of severity of these infections can vary from very benign to severe and even life-threatening. We will also describe infectious and noninfectious complications that can be associated with HIV infection as some migrants might originate from high HIV prevalence countries in sub-Saharan Africa. As the diagnosis and treatment of these diseases can be challenging in certain situations, patients with suspected infection might require referral to specialized centers with experience in their management. Additionally, a brief description of noncommunicable pulmonary diseases will be provided.

Objectives Until recently whole genome sequencing (WGS) for mycobacteria has been restricted mostly to the research setting. However, in 2017 Public Health England has implemented WGS for routine mycobacterial identification and susceptibility testing for Mycobacterium tuberculosis . Our objective was to evaluate the impact of this change on the laboratory turnaround times and availability of results. Methods Over the years 2016 and 2017, the period 1 January to 30 April was selected to represent before and after implementation of WGS. Prior to 2017, line probe assays were used for mycobacterial species identification. Turnaround times for the different steps of the diagnostic process were evaluated for all positive mycobacterial cultures that were sent from our hospital to the Reference Laboratory during the study period. Results A total of 161 positive mycobacterial cultures were sent to the Reference Laboratory. Half of the isolates ( n =81/161, 50%) were M. tuberculosis and 80/161 (50%) were non-tuberculous mycobacteria. The median number of workdays for mycobacterial species identification was 1 day (interquartile range (IQR) 1-3) in 2016 and 6 days (IQR 5-7) in 2017, p M. tuberculosis complex, the median time to drug susceptibility testing results, either molecular or phenotypic, was 12 days (IQR 11-18) in 2016 and 8 days (IQR 7-10) in 2017, p Conclusions Routine WGS performed well in this setting for mycobacterial identification and susceptibility testing for M. tuberculosis and decreased time to drug susceptibility testing results. There was an increase in turnaround times for species identification using WGS, when compared with the previous methods.

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections.

Diagnosing pulmonary tuberculosis (TB) may be delayed until culture results become available.We ascertained the accuracy of a stepwise diagnostic algorithm for the rapid diagnosis of pulmonary TB by GeneXpert from sputum and/or bronchoalveolar lavage (BAL) followed by aMycobacterium tuberculosis-specific BAL ELISPOT assay in patients with a suspected diagnosis of pulmonary TB at a clinical referral centre in Germany.Among 166 patients with a presumptive diagnosis of pulmonary TB, 81 cases were confirmed byM. tuberculosisculture from sputum and/or BAL. In 66 out of 81 (81.5%) cases, patients initially hadM. tuberculosisdetected by GeneXpert from sputum; in addition, six out of 81 (7.4%) cases were diagnosed by GeneXpert on BAL fluid (together 72 out of 81 (88.9%) patients). Out of the remaining nine patients with negative GeneXpert results from sputum and BAL, BAL ELISPOT identified eight patients with culture-confirmed TB correctly (median time to culture positivity 26 days). At a cut-off of >4000 early secretory antigenic target-6- or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 000 0000 lymphocytes, the specificity of the BAL ELISPOT for active TB was 97%.In low TB incidence countries, nearly all patients with active pulmonary TB can be identified within the first few days of clinical presentation using a stepwise strategy with GeneXpert and BAL ELISPOT.

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No evidence that drug-resistant TB results in fewer infections or cases in contacts than drug-susceptible TB http://ow.ly/dgez30f87dr

Introduction : Rapid diagnostic tests (RDT) for HIV infection have high sensitivity and specificity, but in the setting of longstanding antiretroviral therapy (ART), can give false results that can lead to misinterpretation, confusion and inadequate management. The objective of this study was to evaluate the proportion of falsely negative results of a RDT performed on oral fluid in HIV-infected children on longstanding ART. Methods : One hundred and twenty-nine children with known HIV infection and receiving ART were recruited from the HIV Clinic at the Harare Central Hospital, Zimbabwe. HIV testing was performed on oral fluid and on finger-stick blood. Results and Discussion : Children included in the study had a median age of 12 years (IQR 10–14) and 67 (51.9%) were female. Median age at HIV diagnosis was 5 years (IQR 3–6) and the median time on ART was 6.3 years (IQR 4.3–8.1). The oral fluid test was negative in 11 (8.5%) patients and indeterminate in 2 (1.6%). Finger-stick blood test was negative in 1 patient. Patients with a negative oral fluid test had a higher CD4 cell count (967 vs. 723 cells/mm 3 , p = 0.016) and a longer time on ART (8.5 vs. 6 years, p = 0.016). Conclusions : This study found that a substantial proportion of false-negative HIV test results in children on longstanding ART when using an oral fluid test. This could lead to misinterpretation of HIV test results and in the false perception of cure or delayed diagnosis. Keywords HIV; misdiagnosis; rapid diagnostic test; oral fluid test; children (Published: 29 August 2017) Olaru ID et al. Journal of the International AIDS Society 2017, 20 :21751 http://www.jiasociety.org/index.php/jias/article/view/21751 | http://dx.doi.org/10.7448/IAS.20.7.21751

Treatment outcomes for multidrug-resistant (MDR) tuberculosis (TB) are poor with only approximately 50% of patients attaining treatment success [1]. An important driver of treatment failure in many settings is the unavailability of effective drugs for MDR- and extensively drug-resistant (XDR)-TB. Bedaquiline-based therapy leads to high rates of culture conversion in the treatment of MDR-TB

Language barriers are a significant problem for patients with tuberculosis in England and Scotland http://ow.ly/DFjq309KEDT