Specific guidance for setting up antimicrobial stewardship programs in LMICs should be developed. Strategic points might need to be progressively addressed in LMICs, such as (a) ensuring availability of diagnostic testing, (b) providing dedicated education in ABR both for healthcare workers and the general public, (c) creating or strengthening (inter)national agencies towards better regulations and audit on production, distribution and dispensing of drugs, (d) strengthening healthcare facilities, (e) exploring a broader synergism between policy makers, academia, professional bodies and civil society and (f) designing and studying easy and scalable ABS interventions for both hospital and community settings.

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

ObjectiveTo review the effectiveness of antibiotic stewardship interventions in hospitals in low- and middle-income countries.MethodsWe searched MEDLINE®, Embase®, Cochrane Central Register of Controlled Trials and regional indexes for studies of interventions to improve appropriate prescribing and use of antibiotics for hospitalized patients in low- and middle-income countries. We included controlled trials, controlled before-and-after studies and interrupted time-series studies published up to December 2017. We report prescribing, clinical and microbiological outcomes using a narrative approach.FindingsWe screened 7342 original titles and abstracts, assessed 241 full-text articles and included 27 studies from 2 low-income and 11 middle-income countries. We found a medium (11 studies) or high risk (13 studies) of bias. Generally, all types of interventions (structural, persuasive and enabling) and intervention bundles were reported to improve prescribing and clinical outcomes. However, the studied interventions and reported outcomes varied widely. The most frequent intervention was procalcitonin-guided antibiotic treatment (8 of 27 studies, all randomized controlled trials). The intervention was associated with a relative risk for patients receiving antibiotics ranging between 0.40 and 0.87.ConclusionThe majority of studies reported a positive effect of hospital antibiotic stewardship interventions. However, we cannot draw general conclusions about the effectiveness of such interventions in low- and middle-income countries because of low study quality, heterogeneity of interventions and outcomes, and under-representation of certain settings. To strengthen the evidence base, action needs to be taken to address these shortcomings.

BackgroundInformation on causes of death in HIV-infected patients in Sub-Saharan Africa is mainly derived from observational cohort and verbal autopsy studies. Autopsy is the gold standard to ascertain cause of death. We conducted an autopsy study to describe and compare the clinical and autopsy causes of death and contributory findings in hospitalized HIV-infected and HIV-uninfected patients in Uganda.MethodsBetween May and September 2009 a complete autopsy was performed on patients that died on a combined infectious diseases gastroenterology ward in Mulago Hospital in Kampala, Uganda. Autopsy cause of death and contributing findings were based on the macro- and microscopic post-mortem findings combined with clinical information. Clinical diagnoses were reported by the ward doctor and classified as confirmed, highly suspected, considered or not considered, based on information derived from the medical chart. Results are reported according to HIV serostatus.ResultsFifty-three complete autopsies were performed in 66% HIV-positive, 21% HIV-negative and 13% patients with an unknown HIV serological status. Infectious diseases caused death in 83% of HIV-positive patients, with disseminated TB as the main diagnosis causing 37% of deaths. The spectrum of illness and causes of death were substantially different between HIV-positive and HIV-negative patients. In HIV-positive patients 12% of postmortem diagnoses were clinically confirmed, 27% highly suspected, 16% considered and 45% not considered. In HIV-negative patients 17% of postmortem diagnoses were clinically highly suspected, 42% considered and 42% not considered.ConclusionAutopsy examination remains an important tool to ascertain causes of death particularly in settings with limited access to diagnostic testing during life. HIV-positive patients continue to die from treatable and clinically undiagnosed infectious diseases. Until rapid-point of care testing is available to confirm common infections, empiric treatment should be further investigated.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not always confined to the respiratory system, as it impacts people on a broad clinical spectrum from asymptomatic to severe systemic manifestations resulting in death. Further, accumulation of intra-host single nucleotide variants during prolonged SARS-CoV-2 infection may lead to emergence of variants of concern (VOCs). Still, information on virus infectivity and intra-host evolution across organs is sparse. We report a detailed virological analysis of thirteen postmortem coronavirus disease 2019 (COVID-19) cases that provides proof of viremia and presence of replication-competent SARS-CoV-2 in extrapulmonary organs of immunocompromised patients, including heart, kidney, liver, and spleen (NCT04366882). In parallel, we identify organ-specific SARS-CoV-2 genome diversity and mutations of concern N501Y, T1027I, and Y453F, while the patient had died long before reported emergence of VOCs. These mutations appear in multiple organs and replicate in Vero E6 cells, highlighting their infectivity. Finally, we show two stages of fatal disease evolution based on disease duration and viral loads in lungs and plasma. Our results provide insights about the pathogenesis and intra-host evolution of SARS-CoV-2 and show that COVID-19 treatment and hygiene measures need to be tailored to specific needs of immunocompromised patients, even when respiratory symptoms cease.

Background Belgium was among the first countries in Europe with confirmed coronavirus disease 2019 (COVID-19) cases. Since the first diagnosis on February 3rd, the epidemic has quickly evolved, with Belgium at the crossroads of Europe, being one of the hardest hit countries. Although risk factors for severe disease in COVID-19 patients have been described in Chinese and United States (US) cohorts, good quality studies reporting on clinical characteristics, risk factors and outcome of European COVID-19 patients are still scarce. Methods This study describes the clinical characteristics, complications and outcomes of 319 hospitalized COVID-19 patients, admitted to a tertiary care center at the start of the pandemic in Belgium, and aims to identify the main risk factors for in-hospital mortality in a European context using univariate and multivariate logistic regression analysis. Results Most patients were male (60%), the median age was 74 (IQR 61–83) and 20% of patients were admitted to the intensive care unit, of whom 63% needed invasive mechanical ventilation. The overall case fatality rate was 25%. The best predictors of in-hospital mortality in multivariate analysis were older age, and renal insufficiency, higher lactate dehydrogenase and thrombocytopenia. Patients admitted early in the epidemic had a higher mortality compared to patients admitted later in the epidemic. In univariate analysis, patients with obesity did have an overall increased risk of death, while overweight on the other hand showed a trend towards lower mortality. Conclusions Most patients hospitalized with COVID-19 during the first weeks of the epidemic in Belgium were admitted with severe disease and the overall case fatality rate was high. The identified risk factors for mortality are not easily amenable at short term, underscoring the lasting need of effective therapeutic and preventative measures.

Summaryobjective To determine the autopsy acceptance rate and reasons for decline at Mulago Hospital, Kampala, Uganda.methods The next of kin of patients who died in a combined infectious diseases and gastro-enterology ward of Mulago Hospital were approached to answer a questionnaire concerning characteristics of their deceased relative. During the interview their consent was asked to perform a complete autopsy. If autopsy was declined, the next of kin were asked to provide their reason for the decline.results Permission to perform an autopsy was requested in 158 (54%) of the 290 deaths that occurred during the study period. In 60 (38%) cases autopsy was accepted. Fifty-nine autopsies were performed. For 82% of refusals a reason was listed; mainly 'not wanting to delay the burial' (58%), 'no use to know the cause of death' (16%) and 'being satisfied with the clinical cause of death' (10%).conclusion The autopsy rate achieved under study conditions was 38% compared to rates of 5% in Mulago Hospital over the past decade. Timely request and rapid performance of autopsies appear to be important determinants of autopsy acceptance. A motivated team of pathologists and clinicians is required to increase autopsy acceptance.

Blind needle autopsy identified half of the major diagnosis. The addition of ultrasound guidance did not significantly improve the performance of needle autopsy. Needle autopsy is a valuable method to confirm causes of death in HIV-infected patients, especially for highly prevalent diseases like TB.