Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes.Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest.Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths.Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021

Background Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. Methods We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. Findings We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5–14 years, 6·29% (5·05 to 7·70) in those aged 15–49 years, 5·72% (4·02 to 7·39) in those aged 50–69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5–14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15–49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50–69 years, and a 3·29% (–5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (–713 to 2180) fewer deaths. Interpretation Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups

Hematologic abnormalities and associated factors among HIV infected children pre- and post-antiretroviral treatment, North West Ethiopia

Teshome Geletaw, Meseret Zelalem Tadesse, Abayneh Girma Demisse Department of Pediatrics and Child Health, School of Medicine, College of Medicine and Health Science, University of Gondar, Ethiopia Introduction: There are few studies on the hematologic parameters of HIV-infected individuals in Ethiopia; of these, almost all studies researched adults. Our current study is unique in that it mainly focused on the pediatric population and compared both pre- and post-antiretroviral therapy (ART) children. Inference from this study can be used for other developing countries where the burden of HIV disease is high.Objective: The aim of this study was to identify hematologic abnormalities in HIV-infected children before and after initiation of ART.Methodology: A cross-sectional study was conducted on HIV-infected children from June 1 to August 30, 2015. Data were collected using a pretested and structured questionnaire. Statistical analysis was performed using SPSS 20 version.Results: The median age of study subjects was 10 years with an interquartile range (IQR) of (6, 12). Two-thirds (74.3%) of study subjects received ART for >1 year. The median of CD4 count before ART was 490 cells/mm3 with an IQR of (286, 765); this increased to 663 cells mm3 with an IQR of (499, 908) after ART. Likewise, the median of hemoglobin before ART was 11.5 mg/dL with an IQR of (9.9, 13), which increased after ART to 13 mg/dL with an IQR of (11.8, 14). The prevalence of anemia was 42.8% before and 18.9% after ART initiation. The median of absolute neutrophil count before ART was 3×103 with an IQR of (2.1, 4.6) and after ART, it became 3×103 with IQR of (1.9, 4.2). Age <5 years (adjusted odds ratio [AOR]: 2.76; 95% CI: 1.5, 5.0), an advanced stage of AIDS (AOR: 2.8; 95% CI: 1.4, 5.6) and CD4% <25% (AOR: 2.4; 95% CI: 1.2, 4.9) were significantly associated with anemia before ART initiation, while opportunistic infections were associated with anemia after initiation of ART (AOR: 2.3; 95% CI: 1.08, 4.8).Conclusion: ART positively or negatively affects the hematologic profile of HIV-infected children. The current study demonstrated a significant reduction of anemia after initiation of ART. Keywords: anemia, CD4 count, HIV, pediatrics, Gondar&nbsp

Patterns of admission and factors associated with neonatal mortality among neonates admitted to the neonatal intensive care unit of University of Gondar Hospital, Northwest Ethiopia

Abayneh Girma Demisse, Fentahun Alemu, Mahlet Abayneh Gizaw, Zemene Tigabu School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia Introduction: The neonatal period is a highly vulnerable time for an infant completing many of the physiologic adjustments required for life outside the uterus. As a result, there are high rates of morbidity and mortality. The three major causes of mortality in developing countries include prematurity, infection, and perinatal asphyxia. The aim of this study was to identify the patterns of neonatal admission and factors associated with mortality among neonates admitted at the Neonatal Intensive Care Unit (NICU) of University of Gondar Hospital.Materials and methods: A retrospective cross-sectional study was conducted among all admitted neonates in the NICU of University of Gondar referral hospital from December 1, 2015 to August 31, 2016. Information was extracted retrospectively during admission from patient records and death certificates, using a pretested questionnaire. The data were entered and analyzed using SPSS version 20, and p-values <0.05 were considered statistically significant.Results: A total of 769 neonates was included in the study. There were 448 (58.3%) male neonates, and 398 (51.8%) neonates were rural residents. More than two-thirds of the 587 deliveries (76.3%) were performed in tertiary hospitals. Neonatal morbidity included hypothermia 546 (71%), sepsis 522 (67.9%), prematurity 250 (34.9%), polycythemia 242 (31.5%), hypoglycemia 142 (18.5), meconium aspiration syndrome 113 (14.7%), and perinatal asphyxia 96 (12.5%). The overall mortality was 110 (14.3%; 95% confidence interval [CI]: 11.9–16.9) of which 69 (62.7%) deaths occurred in the first 24 hours of age. In the multivariate analysis, mortality was associated with perinatal asphyxia (adjusted odds ratio [AOR]: 5.97; 95% CI: 3.06–11.64), instrumental delivery (AOR: 2.99; 95% CI: 1.08–8.31), and early onset neonatal sepsis (AOR: 2.66; 95% CI: 1.62–6.11).Conclusion: Hypothermia, sepsis, and prematurity were the main reasons for NICU admission. Neonates often died within the first 24 hours of age. Implementing a better referral link and timely intervention could decrease neonatal mortality and morbidities in Gondar, Ethiopia. Keywords: neonatal sepsis, hypothermia, neonatal mortality, neonatal admissio

Perception and experience of clinicians and caregivers in treating childhood severe pneumonia and hypoxemia using bubble continuous positive airway pressure in Ethiopian tertiary and general hospitals.

BACKGROUND: In low and middle-income countries (LMICs), severe pneumonia with hypoxemia is the leading cause of child deaths, even with the provision of WHO-recommended antibiotic therapy, oxygen therapy and other supportive care. Previous studies found positive outcomes from the use of bubble continuous positive airway pressure (bCPAP) for treating these children compared to the standard oxygen therapy. Due to lack of data on the perceptions and experiences of hospital health care workers and caregivers of children on the feasibility and acceptability of bCPAP in treating children with severe pneumonia and hypoxemia in real-life settings, we examined these issues in tertiary and general hospitals in Ethiopia. METHODS: As part of a three-stages clinical trial, this qualitative study was conducted in two tertiary (stage I) and two general (stage II) hospitals from September 2019 to July 2020. During stages I and II, we have consecutively enrolled children with severe pneumonia and hypoxemia and put them on bCPAP to examine its feasibility and acceptability by clinicians and parents. A total of 89 children were enrolled (49 from two tertiary and 40 from two general hospitals). Then qualitative data were collected through 75 repeated in-depth interviews by social-science experts with purposively selected 30 hospital health workers and 15 parents of 12 children who received bCPAP oxygen therapy in the hospitals. Interview data were supplemented by 6 observations in the hospitals. Data were analyzed using a thematic approach. RESULTS: Identified structural and functional challenges for the introduction of bCPAP in treating childhood severe pneumonia and hypoxemia in the study hospitals include: inadequate number of pulse oximeters; unavailability of nasal prongs with age-specific size; inadequate and non-functioning oxygen flow meters, concentrator, and cylinders; disruption in power-supply; and inadequate number of staff. The opportunities in introducing bCPAP oxygen therapy included the availability of a dedicated corner for the study patients situated in front of nurse's station, required medicines and satisfactory level of clinicians' knowledge and skills for treating severe pneumonia patients. Additionally, the identified operational challenges were occasional lack of bubbling in the water-filled plastic bottle, lack of stand for holding the water-filled plastic bottle, and delayed shifting of oxygen source from an oxygen concentrator to a cylinder, particularly during electricity disruption. Participants (clinicians and parents) expressed their satisfaction as bCPAP oxygen therapy was found to be simple to handle, children had ease of breathing and recovered fast without major ill effects. CONCLUSION: Our study identified some important structural, functional, and operational challenges that need to be addressed before implementation of bCPAP oxygen therapy especially in frontline general hospitals with limited resources. In spite of these observed challenges, the clinicians and caregivers were highly satisfied with the overall performance of bCPAP oxygen therapy