Epidemiology and Outcomes of Critical Illness and Novel Predictors of Mortality in an Ethiopian Medical Intensive Care Unit.

Low- and middle-income countries (LMICs) bear most of the global burden of critical illness. Managing this burden requires improved understanding of epidemiology and outcomes in LMIC intensive care units (ICUs), including LMIC-specific mortality prediction scores. This study was a retrospective observational study at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, examining all consecutive medical ICU admissions from June 2014 to April 2015. The primary outcome was ICU mortality; secondary outcomes were prolonged ICU stay and prolonged mechanical ventilation. ICU mortality prediction models were created using multivariable logistic regression and compared with the Mortality Probability Model-II (MPM-II). Associations with secondary outcomes were examined with multivariable logistic regression. There were 198 admissions during the study period; mortality was 35%. Age, shock on admission, mechanical ventilation, human immunodeficiency virus, and Glasgow Coma Scale ≤8 were associated with ICU mortality. The receiver operating characteristic curve for this 5-factor model had an AUC of 0.8205 versus 0.7468 for MPM-II, favoring the simplified new model. Mechanical ventilation and lack of shock were associated with prolonged ICU stays. Mortality in an LMIC medical ICU was high. This study examines an LMIC medical ICU population, showing a simplified prediction model may predict mortality as well as complex models.

Effectiveness of a bedaquiline, linezolid, clofazimine "core" for multidrug-resistant tuberculosis.

Rationale: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients. Objectives: We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline. Methods: We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment. Measurements and Main Results: Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41). Conclusions: High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs.

Risk factors and determinants of pulmonary function impairments in chronic respiratory diseases in Ethiopia: A hospital-based cross-sectional study

Introduction: Chronic respiratory diseases (CRDs) are diseases of the lung airways and parenchyma. Globally, they are the leading causes of morbidity and mortality. This study aimed to characterize the common CRDs, along with their lung function and possible determinants in symptomatic patients attending Bishoftu General Hospital, Ethiopia. Methods: A cross-sessional study was conducted at the outpatient of Bishoftu Hospital, Ethiopia from June 2019 to March 2020. Consecutive adult patients aged 18 and above with CRDs (≥8 weeks) were recruited. Questionnaires were used to collect data on demographics, symptoms, diagnoses, and putative risk factors. Lung function was measured by spirometry. Result: A total of 170 participants were recruited, the majority 102(60.0%) were female. The mean age was 49 years (SD=16). The most common symptoms were wheezing in the last twelve months 156 (91.8%), cough 138 (81.2%), and severe exertional breathlessness 137 (80.6%). Thirty-nine (22.9%) were either active or passive smokers. Half of the patients (50.3%) were exposed daily to vapors, dust, gases, or fumes and 58 (34.3%) were exposed to biomass smoke. In total, 138 (81.2%) had a positive allergen skin prick test. Chronic bronchitis (49.1%) and asthma (36.1%) were the most common clinical diagnoses. Classification of lung function revealed 23 (15%) normal, 29 (19%) obstructive, 36(23.5%) restrictive and 61(39.9%) mixed patterns. Airflow obstruction was independently associated with increasing age (p<0.05), exertional breathlessness (p<0.001), previous history of asthma (p<0.05), BMI (p<0.05), and doctor-diagnosed chronic obstructive pulmonary disease (p<0.001) and asthma (p<0.05). Conclusion: This study shows a high burden of abnormal lung function in patients attending clinics because of CRDs symptoms. These findings support the critical need for spirometry services to determine lung abnormality in patients with chronic respiratory symptoms.

Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis.

Rationale: Current recommendations for the treatment of rifampicin- and multidrug-resistant tuberculosis include bedaquiline (BDQ) used for 6 months or longer. Evidence is needed to inform the optimal duration of BDQ. Objectives: We emulated a target trial to estimate the effect of three BDQ duration treatment strategies (6, 7-11, and ⩾12 mo) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis. Methods: To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse probability weighting. Measurements and Main Results: The 1,468 eligible individuals received a median of 4 (interquartile range, 4-5) likely effective drugs. In 87.1% and 77.7% of participants, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment was 0.85 (95% confidence interval [CI], 0.81-0.88) for 6 months of BDQ, 0.77 (95% CI, 0.73-0.81) for 7-11 months, and 0.86 (95% CI, 0.83-0.88) for ⩾12 months. Compared with 6 months of BDQ, the ratio of treatment success was 0.91 (95% CI, 0.85-0.96) for 7-11 months and 1.01 (95% CI, 0.96-1.06) for ⩾12 months. Naive analyses that did not account for bias revealed a higher probability of successful treatment with ⩾12 months (ratio, 1.09 [95% CI, 1.05-1.14]). Conclusions: BDQ use beyond 6 months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time bias can influence estimates of the effects of treatment duration. Future analyses should explore the effect of treatment duration of BDQ and other drugs in subgroups with advanced disease and/or receiving less potent regimens.

Rationale and design of a screening study to detect schistosomiasis-associated pulmonary hypertension in Ethiopia and Zambia.

Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH) worldwide, but the prevalence and risk factors for schistosomiasis-associated PAH (SchPAH) development are not well understood. Schistosomiasis-associated hepatosplenic disease (SchHSD) is thought to be a major risk factor for PAH development. Herein, we describe our plans for prospectively screening SchHSD subjects for clinical evidence of PAH at two major academic medical centers and national referral hospitals in Addis Ababa, Ethiopia and Lusaka, Zambia. The screening study will primarily be conducted by echocardiography, in addition to clinical assessments. Plasma samples will be drawn and banked for subsequent analysis based on preclinical animal model rationale. If successful, this study will demonstrate feasibility of conducting prospective cohort studies of SchPAH screening in schistosomiasis-endemic regions of Africa, and provide initial data on clinic-based disease prevalence and potential mechanistic biomarkers underlying disease pathogenesis.

Clinical Characteristics and Molecular Profiles of Lung Cancer in Ethiopia.

INTRODUCTION: Lung cancer is the most common cause of cancer deaths worldwide, accounting for 1.8 million deaths each year. Only 20% of lung cancer cases are reported to occur in low- and middle-income countries. An estimated 1.5% of all Ethiopian cancers involved the lung; however, no nationwide cancer registry exists in Ethiopia. Thus, accurate data on clinical history, histopathology, molecular characteristics, and risk factors for lung cancer are not available. The aim of this study was to describe the clinical, radiologic, and pathologic characteristics, including available molecular profiles, for lung cancer at Tikur Anbessa Specialized Hospital (TASH), the main tertiary referral center in Addis Ababa, Ethiopia. METHODS: A cross-sectional study was conducted at TASH among 146 patients with pathologically confirmed primary lung cancer, diagnosed from 2015 to 2019 and recorded in the Addis Ababa Cancer Registry at TASH. Clinical data were extracted from patient medical records, entered into a Research Electronic Data Capture database, and analyzed using Statistical Package for the Social Sciences statistical software. Variables collected included sociodemographics, personal exposures, comorbidities, clinical manifestations at presentation, chest imaging results, diagnostic procedures performed, histopathological classification, cancer staging, and type of treatment (if any). A subset of lung biopsies fixed in formalin for 2 to 7 days, which could be retrieved from the files of the Pathology Department of TASH, were reviewed, and molecular analysis was performed using next-generation sequencing to identify the tumor-oncogenic drivers. RESULTS: Among the 146 patients studied, the mean (SD) age was 54 plus or minus 13 years; 61.6% (n = 90) were male and 25.3% (n = 37) had a history of tobacco use. The most common clinical manifestations included cough (88.4%, n = 129), chest pain (60.3%, n = 88), and dyspnea (53.4%, n = 78). The median duration of any symptoms was 6 months (interquartile range: 3-12 mo). The most common radiologic features were lung mass (84.9%, n = 129) and pleural effusion (52.7%, n = 77). Adenocarcinoma accounted for 35.7% of lung cancers (n = 52) and squamous cell carcinoma 19.2% (n = 28) from those specimens was reported. Among patients on whom staging of lung cancer was documented, 92.2% (n = 95) of the subjects presented at advanced stages (stages III and IV). EGFR mutation, exons 19 and 20, was found in 7 of 14 tissue blocks analyzed. No specific risk factors were identified, possibly reflecting the relatively small sample size and limited exposures. CONCLUSIONS: There are marked differences in the presentation, risk factors, and molecular characteristics of lung cancer in Ethiopia as compared with other African and non-African countries. Adenocarcinoma was the most common histologic type of lung cancer detected in our study, similar to findings from other international studies. Nevertheless, compared with high-income countries, lung cancer in Ethiopia presents at a younger age, a later stage, and without considerable personal tobacco use. The relatively higher prevalence of EGFR mutation, from the limited molecular analyses, suggests that factors other than smoking history, such as exposure to biomass fuel, may be a more important risk factor. Country-specific screening guidelines and treatment protocols, in addition to a national tumor registry and greater molecular mutation analyses, are needed to improve prevention and management of lung cancer in Ethiopia.

Creating a specialist physician workforce in low-resource settings: reflections and lessons learnt from the East African Training Initiative.

Many African countries have extremely low ratios of physicians to population, and there are very, very few specialists. This leaves most patients without access to specialised care, and importantly also leaves many countries with insufficient expertise to properly evaluate the burden of illness and the needs of the population overall. The challenges to training a specialised physician workforce in resource-limited settings are many, and they go far beyond the (relatively simple) task of transmission of clinical skills. We initiated a capacity-building programme to train pulmonary physicians in Ethiopia, a country of 105 million persons with a high burden of lung disease that had no prior existing training programme in pulmonary medicine. Using volunteer faculty from the USA and Europe, we have provided high-quality training and established a cohort of pulmonary specialists there. We have identified several components of training that go beyond clinical skills development but which we feel are crucial to sustainability. These components include the delineation of viable career pathways that allow professional growth for subspecialist physicians and that support the permanent establishment of a local faculty; the development of important non-clinical skills, including leadership and pedagogical techniques; training in clinical research methodologies; and the development of mechanisms to amplify the impact of a still relatively small number of specialised physicians to address the needs of the population generally. Our programme, the East African Training Initiative, has successfully addressed many of these challenges and we hope that it can be replicated elsewhere.

Epidemiology of trachoma and its implications for implementing the "SAFE" strategy in Somali Region, Ethiopia: results of 14 population-based prevalence surveys.

PURPOSE: Ethiopia is highly trachoma endemic. Baseline mapping was needed in Ethiopia's Somali Region to guide elimination efforts. METHODS: Cross-sectional community-based surveys were conducted in 34 suspected trachoma-endemic woredas, grouped as 14 evaluation units (EUs), using a standardised mapping methodology developed for the Global Trachoma Mapping Project. RESULTS: In total, 53,467 individuals were enumerated. A total of 48,058 (89.9%) were present at the time of survey teams' visits and consented to examination. The prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years ranged from 4.1% in the EU covering Danot, Boh, and Geladin woredas in Doolo Subzone to 38.1% in the EU covering Kebribeyah and Hareshen woredas in Fafan Subzone (East). The trichiasis prevalence among adults aged over 15 years varied from 0.1% in the EU covering Afder, Bare, and Dolobay woredas in Afder Subzone (West) to 1.2% in the EU covering Awbere in Fafan Subzone (West). CONCLUSION: Mass drug administration (MDA) with azithromycin is needed in 13 EUs (population 2,845,818). Two EUs (population 667,599) had TF prevalences in 1-9-year-olds of ≥30% and will require at least 5 years of MDA; 5 EUs (population 1,1193,032) had TF prevalences of 10-29.9% and need at least three years of MDA; 6 EUs (population 985,187) had TF prevalences of 5-9.9% and need at least one round of azithromycin distribution before re-survey. In all 13 of these EUs, implementation of facial cleanliness and environmental improvement measures is also needed. Surveys are still needed in the remaining 34 unmapped woredas of Somali Region.

Level of asthma control and risk factors for poor asthma control among clinic patients seen at a Referral Hospital in Addis Ababa, Ethiopia.

OBJECTIVE: Uncontrolled asthma negatively impacts patients, families, and the community. The level of symptom control among asthmatics in Ethiopia has not been well studied. We investigated the level of asthma control and risk factors for poor asthma control in clinic patients seen in the largest public hospital in Ethiopia. RESULTS: In this cross-sectional study, we studied all 182 consecutive subjects with a physician diagnosis of asthma who were seen in chest clinic at Tikur Anbessa Specialized Hospital between July and December 2015. Of the 182 subjects, 68.1% were female. The mean age was 52 ± 12 years and the median duration of asthma was 20 ± 12.7 years. One hundred and seventeen subjects (64.3%) had nighttime awakening due to asthma. Fifty-eight (31%) were not using controller medications and 62 (34.6%) had improper inhaler technique. Only 44 (24.2%) subjects had well-controlled asthma. On multivariate analysis, variables associated with uncontrolled asthma included: use of biomass fuel for cooking, longer duration of asthma (> 30 year), incorrect inhalation technique, and asthma exacerbation in the last 12 months. Most asthmatics attending in the largest public hospital in Ethiopia, had uncontrolled asthma. Several risk factors for poor asthma control were identified. Improved asthma control is possible through directed interventions.

SEQUELAE OF PATIENTS TREATED FOR PULMONARY TUBERCULOSIS IN CHEST CLINIC, TIKUR ANBESSA SPECIALIZED HOSPITAL (TASH), ADDIS ABABA, ETHIOPIA.

BACKGROUND: Pulmonary tuberculosis (PTB) is one of the most common infectious diseases worldwide, and contributes significantly to morbidity and mortality in developing countries. Despite availability of effective treatment, a significant number of patients suffer from permanent lung damage, which predisposes patients to numerous pulmonary complications. OBJECTIVE: To assess chronic sequelae of patients treated for PTB in a chest clinic at Tikur Anbessa Hospital. METHODS: This was a retrospective, cross-sectional analysis of patients registered in a clinical database at the chest clinic of Tikur Anbessa specialized Hospital between January and December 2013. Patients with a history of pulmonary tuberculosis treatment were identified and included in the analysis. RESULTS: Among all patients having follow-up at the chest clinic of TASH during the study period, 134 (18.5%) presented with chronic pulmonary complications of TB. Seventy two patients (54%) were male, and the mean and median ages were 40 and 37 years, respectively. Of the study population, 83 (61.9%) patients had clinically significant parenchymal scarring and fibrosis, 40 (29.9%) had bronchiectasis, 5(3.7%) had Aspergilloma, 4(3%) had granuloma/calcification, one patient (0.7%) had pleural thickening, and one patient (0.7%) underwent pneumonectomy during the study period. CONCLUSIONS: Fibrosis and bronchiectasis were the most common pulmonary complications of tuberculosis among patients encountered at the TASH chest clinic during the study period. This demonstrates the impact of pulmonary tuberculosis is beyond management of active disease.