Development of a protocol for assessing the role of WASH in AMR distribution in the environment

Resistance in Malawi and Uganda (DRUM) consortium to measure the role of WASH in the transmission and control of AMR Abstract In Low and Middle Income countries (LMICs), there is a high incidence of severe bacterial infection, a critically inadequate health system infrastructure to diagnose and treat bacterial infections and widespread and uncontrolled availability of antimicrobials. This situation causes both a huge burden of morbidity and mortality, and is increasing selective pressure for the emergence of antimicrobial resistance (AMR) in pathogens. As LMICs will be the last to benefit from new classes of antimicrobials it is therefore urgent to undertake research addressing AMR in LMICs that aims to identify drivers and interrupt transmission of AMR determinants responsible. Exposures associated with WASH are integral to enteric bacteria and AMR transmission. AMR elements have been found in water, faeces and wastewater in LMICs, and this is compounded by a lack of faecal management (e.g. open defaecation, lack of access to faecal sludge management) and multiple uses of water (e.g. washing, irrigation, animal management and drinking). These factors contribute to community borne AMR transmission, and must be considered across multiple exposure pathways within the community. Focused in urban, peri-urban and rural settings in Malawi and Uganda, the Drivers of Antimicrobial Resistance in Uganda and Malawi (DRUM) consortium is an interdisciplinary programme funded by the Medical Research Council (2018 – 2021). The study aims to address three key questions (1) What are the drivers of ESBL E. coli and ESBL Klebsiella pneumoniae transmission in Uganda and Malawi?; (2) What are the critical points at which efforts to interrupt human AMR acquisition are likely to have the greatest impact?; and (3) Which strategies are likely to be most affordable and feasible to societies and how far is this specific to context? The research will develop agent-based models to enable us to predict how these transmission pathways can be interrupted. Data will be collated on a range of issues including: antibiotic use; antibiotic availability; illness; household demographics; and environmental contamination using both qualitative and quantitative methods. Key to this model will be the under researched area of AMR and WASH. This will develop a clear understanding of water, sanitation and hygiene (WASH) infrastructure and practices both domestically and institutionally [transect walks n=8; observations and checklists at household n=255; institutions n=50], identify the underlying influences on current practices [in depth interviews n=75; key informant interviews n=50; behavioral determinant questionnaires n=500; focus group discussions n=25] and identify drivers which may be amenable to change. These methods will be described in detail. Data will be collected with extensive environmental sampling to identify the transmission routes, support the design of the model and inform interventions. Existing national and international policies in the WASH sector do not currently consider AMR, and the production of evidence in this area is key to supporting and driving policy integration and uptake

The Teacher Wars: A History of America’s Most Embattled Profession

The Teacher Wars: A History of America’s Most Embattled ProfessionDana GoldsteinNew York: Doubleday, 2014, 349 p.Dana Goldstein je novinarka i spisateljica te dobitnica nekoliko cijenjenih stipendija na području novinarstva. Piše o obrazovanju, ženskim pitanjima, nejednakosti i kaznenom pravosuđu. Njena knjiga „The Teacher Wars“ u kojoj pokriva 175 godina povijesti američkog školstva postala je bestseler New York Timesa što je učinilo Goldstein jednom od najcjenjenijih mladih novinarki u Sjedinjenim Američkim Državama. Knjiga je podijeljena na uvod, deset poglavlja, epilog, zahvalu, bilješke, odabranu bibliografiju i indeks. Više od petsto primarnih i sekundarnih izvora koje je autorica koristila navedeno je u bilješkama, dok u odabranoj bibliografiji donosi, organizirane prema temi, samo one izvore koje je najviše upotrebljavala što daje vrijedan pregled literature iz ovog područja. U sredini knjige nalaze se i fotografije povijesnih ličnosti i događaja čiju ulogu u razvoju američkog školstva Goldstein opisuje.</p

Linezolid for drug-resistant tuberculosis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy of linezolid when used as part of a second-line regimen for treating people with multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) pulmonary tuberculosis (TB), and to assess the prevalence and severity of adverse events associated with linezolid use in this patient grou

Community exposure assessment to anti-microbial resistance (AMR); case study of Malawi

Anti-microbial resistance is currently one of the greatest global health threat (CDC, 2020, WHO, 2020). Efforts have previously focused on the healthcare sector through antibiotic stewardship and surveillance (Cueni, 2020). Poor water, sanitation and hygiene (WASH) practices and infrastructure contribute to the transmission of resistant bacteria (Iskandar et al., 2020). Low-and middle-income countries (LMICs) such as Malawi have pre-existing WASH challenges, which increase the risk of population exposure to AMR (Cassivi et al., 2020). There is an existing knowledge gap regarding the prevalence of AMR in the wider community environment (Ahammad et al., 2018)

An integrated model of care for neurological infections: the first six years of referrals to a specialist service at a university teaching hospital in Northwest England

Background A specialist neurological infectious disease service has been run jointly by the departments of infectious disease and neurology at the Royal Liverpool University Hospital since 2005. We sought to describe the referral case mix and outcomes of the first six years of referrals to the service. Methods Retrospective service review. Results Of 242 adults referred to the service, 231 (95 %) were inpatients. Neurological infections were confirmed in 155 (64 %), indicating a high degree of selection before referral. Viral meningitis (35 cases), bacterial meningitis (33) and encephalitis (22) accounted for 38 % of referrals and 61 % of confirmed neurological infections. Although an infrequent diagnosis (n = 19), neurological TB caused the longest admission (median 23, range 5 – 119 days). A proven or probable microbiological diagnosis was found in 100/155 cases (64.5 %). For the whole cohort, altered sensorium, older age and longer hospital stay were associated with poor outcome (death or neurological disability); viral meningitis was associated with good outcome. In multivariate analysis altered sensorium remained significantly associated with poor outcome, adjusted odds ratio 3.04 (95 % confidence interval 1.28 – 7.22, p = 0.01). Conclusions A service of this type provides important specialist care and a focus for training and clinical research on complex neurological infections

A novel ESBL colilert system for environmental surveillance of AMR bacteria at markets in LMICs

The spread of ESBL-producing bacteria through environmental compartments needs to be quantified to understand the drivers of resistant infections caused by ESBL bacteria, including the examination of water as a possible transmission pathway1. Effective methods to assess environmental contamination by ESBL-producing bacteria are critical to enable rapid and reliable testing in LMIC settings, and ideally, they should be simple, cost effective and utilize current infrastructure. We present findings from an adaption of an ESBL IDEXX Colilert system, developed by the Centers for Disease Control and Prevention (CDC)2, for the identification and quantification of ESBL contamination in four urban Malawian markets

First case report of a successfully managed severe COVID-19 infection in Malawi

The coronavirus disease 2019 (COVID-19) pandemic is now established on the African continent, with cases rapidly increasing in Malawi (1742 confirmed cases and 19 deaths as of 5 July 20201). Clinicians require guidelines, deliverable in the Malawi context, to effectively and safely treat patients for the best possible outcome. In Malawi, key public messages around social distancing, hand washing and shielding for at-risk individuals have been widely distributed by the Ministry of Health. However, it has not been possible to implement strict lockdown measures in Malawi due to the risk of widespread economic disruption, hunger, worsened food insecurity, risk of violence and mass political rallies. Testing rates are low such that the number of confirmed cases in Malawi is likely to significantly under-represent the actual number of cases. As the epidemic unfolds, it is vital that doctors implement standardised case management guidelines to improve survival for patients who require hospital admission. The majority of patients hospitalised with COVID-19 require medical-ward level care, including provision of adequate oxygen3. Increased oxygen provision has been a major focus of COVID-19 preparedness activities in Malawi

Lessons learnt from the rapid implementation of reusable personal protective equipment for COVID-19 in Malawi

The SARS-CoV-2 pandemic has challenged health systems and healthcare workers worldwide. Access to personal protective equipment (PPE) is essential to mitigate the risk of excess mortality in healthcare providers. In Malawi, the cost of PPE represents an additional drain on available resources. In the event of repeated waves of disease over several years, the development of sustainable systems of PPE is essential. We describe the development, early implementation and rapid scale up of a reusable gown service at a tertiary-level hospital in Blantyre, Malawi. Challenges included healthcare worker perceptions around the potential of reduced efficacy of cotton gowns, the need to plan for surge capacity and the need for ongoing training of laundry staff in safety and hygiene procedures. Benefits of the system included increased coverage, decreased cost and reduced waste disposal. The implementation of a reusable cotton gown service is feasible, acceptable and cost-effective in tertiary centres providing specialist COVID-19 care at the height of the pandemic. This innovation could be expanded beyond low-income settings

Circumstances for treatment and control of invasive Enterobacterales infections in eight hospitals across sub-Saharan Africa: a cross-sectional study

BACKGROUND: Bloodstream infections caused by Enterobacterales show high frequency of antimicrobial resistance (AMR) in many Low- and Middle-Income Countries. We aimed to describe the variation in circumstances for management of such resistant infections in a group of African public-sector hospitals participating in a major research study. METHODS: We gathered data from eight hospitals across sub-Saharan Africa to describe hospital services, infection prevention and antibiotic stewardship activities, using two WHO-generated tools. We collected monthly cross-sectional data on availability of antibiotics in the hospital pharmacies for bloodstream infections caused by Enterobacterales. We compared the availability of these antibiotics to actual patient-level use of antibiotics in confirmed Enterobacterales bloodstream infections (BSI). RESULTS: Hospital circumstances for institutional management of resistant BSI varied markedly. This included self-evaluated infection prevention level (WHO-IPCAF score: median 428, range 155 to 687.5) and antibiotic stewardship activities (WHO stewardship toolkit questions: median 14.5, range 2 to 23). These results did not correlate with national income levels. Across all sites, ceftriaxone and ciprofloxacin were the most consistently available antibiotic agents, followed by amoxicillin, co-amoxiclav, gentamicin and co-trimoxazole. There was substantial variation in the availability of some antibiotics, especially carbapenems, amikacin and piperacillin-tazobactam with degree of access linked to national income level. Investigators described out-of-pocket payments for access to additional antibiotics at 7/8 sites. The in-pharmacy availability of antibiotics correlated well with actual use of antibiotics for treating BSI patients. CONCLUSIONS: There was wide variation between these African hospitals for a range of important circumstances relating to treatment and control of severe bacterial infections, though these did not all correspond to national income level. For most antibiotics, patient-level use reflected in-hospital drug availability, suggesting external antibiotics supply was infrequent. Antimicrobial resistant bacterial infections could plausibly show different clinical impacts across sub-Saharan Africa due to this contextual variation

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study

Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa