A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis.

Background: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. Objective: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Methods: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. Results: A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 - 0.84). Conclusions: We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted.

Antimicrobial resistance profiles of bacterial isolates from clinical specimens referred to Ethiopian Public Health Institute: analysis of 5-year data.

BACKGROUND: Antimicrobial resistance is one of the common global public health problems. The emergence of antimicrobial resistance is multifactorial, and tackling its development is challenging. Consequently, infections caused by resistant bacteria are unresponsive to conventional drugs, resulting in prolonged and severe illnesses, higher mortality rates, and considerable healthcare costs. Therefore, understanding the antimicrobial resistance profiles of bacterial pathogens is essential to optimize treatments and reduce the risks associated with infections. This study aimed to determine the antimicrobial resistance patterns of bacterial isolates from different clinical specimens at the Ethiopian Public Health Institute (EPHI). MATERIALS AND METHODS: The retrospective cross-sectional study was conducted on the bacterial culture and antibiotic susceptibility reports of different clinical specimens referred to the Bacteriology Laboratory of EPHI from September 2015 to August 2019. Standard bacteriological techniques were used for the isolation and identification of the bacteria. Data were extracted from 840 patients' records, which included the type of clinical sample cultured, the name of the bacteria, the representations of the antibiotics used for susceptibility testing, and the susceptibility results. Descriptive statistics were used to describe the bacterial isolates and the antimicrobial resistance profiles. RESULTS: Eight types of clinical specimens were analyzed for bacterial isolates and urine specimens were the most analyzed. Ten different genera of bacteria were identified by culture. Almost all the isolates were gram-negative bacteria, while only one species of gram-positive (Staphylococcus aureus) was reported. Antibiotic sensitivity patterns were tested on 840 culture isolates. Escherichia coli strains revealed more than 57% resistance to seventeen antibiotics. Klebsiella pneumoniae showed nearly 70% or greater resistance rates for 17 of the antibiotics used. The overall detected multidrug resistance (MDR) was 64.29%. The highest MDR was reported in Acinetobacter strains (84%) followed by K. pneumoniae (80%). CONCLUSIONS: The multidrug resistance rates found in this study were alarming. Strengthening antimicrobial resistance surveillance at the national level is mandatory, and antimicrobial sensitivity testing should be accessible at local diagnostic centers.

Intestinal helminth co-infection and associated factors among pulmonary tuberculosis patients in Africa and Asia: a systematic review and meta-analysis.

INTRODUCTION: Tuberculosis (TB) and intestinal helminths have huge public health importance, and they are geographically overlapped. Data about the burden of intestinal helminth and TB co-infection in these areas are fragmented. In this systematic review and meta-analysis we compile the current literatures and generate pooled prevalence. We also identity factors associated with intestinal helminth co-infection among TB patients. METHODS: Original articles published in English language up to March 23, 2022 were systematically searched from electronic database (PubMed/Medline, Scopus, Science Direct, Google Scholars and HINARI). The search was done using medical subject heading terms and keywords. Identified articles were exported into the EndNote library. The identified articles were screened using PRISMA flow diagram. Then the methodological quality of included articles was evaluated and rated using the modified version of Newcastle-Ottawa Scale. Data were extracted using Microsoft Excel. Sensitivity analysis and Egger regression test were used for the assessment of heterogeneity and publication bias. Finally the results are presented with a meta-analysis of pooled estimates, forest plots, and tables. The quantitative data were analyzed using Stata version 14. RESULTS: From a total of 5457 searched articles, 22 eligible articles were included in the review. The pooled prevalence of helminth co-infection among TB cases was 29.69% (95%CI: 21.10, 38.29). TB patients were found to more frequently harbor one or more intestinal helminths than TB negative individuals (OR = 1.72 (95%CI: 1.20, 2.48)). Among the reported helminths, Schistosoma mansoni and Strongyloides stercoralis had the highest pooled prevalence among TB cases. However, unlike other individual helminths, only Strongyloides stercoralis (OR = 2.67 (95% CI, 1.20-6.76)) had significant association with TB cases compared to TB negatives. BMI was significantly associated with intestinal helminth co-infection among TB patients (OR = 2.75 (95%CI: 1.19, 6.38)). CONCLUSIONS: Patients with TB have been shown to harbor co-infection with one or more intestinal helminths with considerable proportions when compared with TB-negative individuals. The higher prevalence of helminth infection in TB cases might indicate that co-infection promotes active TB disease. Thus, routine intestinal helminth screening and assessment of their nutritional status is suggested for TB patients.

Genetic diversity and drug sensitivity profile of Mycobacterium tuberculosis among children in Ethiopia.

BACKGROUND: Worldwide, tuberculosis (TB) affects about one million children every year. The burden of the disease is higher in developing countries. However, there is limited information on the lineages and drug sensitivity patterns of Mycobacterium tuberculosis (M. tuberculosis) infecting children in these countries, including Ethiopia. Thus, this study aimed to characterize the different lineages of the M. tuberculosis complex causing childhood pulmonary tuberculosis and evaluate the drug-sensitivity patterns to the first-line anti-TB drugs. METHOD: A total of 54 stored cultures were used in this study. The region of difference 9 (RD9) based polymerase chain reaction (PCR) and spoligotyping were employed for the identification of the isolates at the species and lineages level respectively. Lineage identification was done by using the pre-existing database. Identification of clustering of the spoligotype patterns was by using the SPOLIDB3-based model. The result was retrieved by the most probable family format. Furthermore, the phenotypic, and genotypic drug-sensitivity test (DST) was performed using Mycobacterium Growth Indicator Tube (MGIT™ 960) and GenoTypeMTBDRplus assay respectively. Data analysis was done using SPSS version 27 software. RESULT: Spoligotyping produced 39 interpretable results for M. tuberculosis. The majority (74.4%) of them were clustered into 7 groups, while the rest (25.6%) were single. The Euro-American (EA) lineage was the predominant lineage (64.1%) followed by the East-African Indian (EAI) (30.8%) and M. Africanum (5.1%) lineages. The most predominant subtypes were SIT37 (15.4%), SIT149 (12.8%), SIT25 (7.7%), and SIT53 (7.7%). Furthermore, of the identified SITs, T1 and CAS families consisted of 38.5% and 28.2% of the lineages respectively. Drug susceptibility was 91.9% by phenotypic method and 97.4% by molecular assay. The overall prevalence of any resistance was 7.8% and there was a single MDR-TB. CONCLUSION: Many of the isolates belong to the modern lineages (Euro American) representing the most common circulating strains in the country. More importantly, despites the tiny isolates tested, drug resistance is low. To fully describe the molecular epidemiology of MTBC lineages in children, we recommend a prospective large-scale study.

Parasitological and malacological surveys to identify transmission sites for Schistosoma mansoni in Gomma District, south-western Ethiopia.

Schistosomiasis is a neglected tropical disease that disproportionately affects the poorest people in tropical and subtropical countries. It is a major parasitic disease causing considerable morbidity in Ethiopia. Despite significant control efforts, schistosomiasis transmission is still widespread in many rural areas of the country. The aim of this study was to determine the prevalence and intensity of intestinal schistosomiasis among schoolchildren, as well as to identify schistosomiasis transmission sites in Gomma District, southwestern Ethiopia. Between October 2018 and September 2019, cross-sectional parasitological and malacological surveys were conducted in the study area. The study comprised 492 school-children aged 6 to 15 years old from four primary schools in Gomma District. To identify and quantify eggs of Schistosoma mansoni from the children, stool specimens were collected and processed using double Kato-Katz thick smears. Water bodies adjacent to human settlements in the study area were surveyed for snail intermediate hosts of S. mansoni. Morphological identification of collected snails was conducted, followed by examining their infection status using a dissecting microscope. The overall prevalence of S. mansoni infection was 73.8% (95%CI: 69.9-77.7%) and 41.6% of them had moderate-to-heavy infections. The prevalence of S. mansoni infection differed considerably by age group, with the older age groups (12-15) having a higher prevalence than the younger age groups (6-11) (p < 0.001). The prevalence of infection also varied significantly among schools; Dedo Ureche had the highest prevalence (86.9%) (p = 0.034), while Goga Kilole had relatively the lowest prevalence of S. mansoni infection (59.6%) (p = 0.003). A total of 1463 Biomphalaria pfeifferi snails were collected from 11 survey sites throughout the study area, with 357 (24.4%) of the snails shedding schistosomes cercariae. Despite intensified efforts to scale up mass drug administration in Ethiopia, this study reported high levels of S. mansoni infection among schoolchildren and snail intermediate hosts in rural communities in Gomma. Such a high infection rate warrants pressing needs for targeted and integrated interventions to control the disease in the area.

Cellular and Cytokine Responses in Lymph Node Granulomas of Bacillus Calmette Guérin (BCG)-Vaccinated and Non-vaccinated Cross-Breed Calves Naturally Infected With Mycobacterium bovis.

Local immunological responses at the site of infections, such as at the lymph nodes and lungs, do play a role in containing infection caused by Mycobacterium bovis (M. bovis). This bovine tuberculosis (bTB) study was conducted to evaluate cellular and cytokine responses in the lymph nodes and lungs of BCG-vaccinated and non-vaccinated calves that were naturally infected with M. bovis. Immunohistochemical assays were used for examination of the responses of macrophages, T cells, cytokines and chemical mediators of 40 (22 vaccinated and 18 non-vaccinated) Holstein-Friesian-zebu crossbred calves that were naturally exposed for 1 year to a known bTB positive cattle herd. The incidence rates of bTB visible lesion were 68.2% (15/22) and 89% (16/18) in vaccinated and non-vaccinated calves, respectively. The local responses of CD4+ and CD8+ T cells, and those of IFN-γ and TNF-α within the lesions, were stronger (P < 0.05) in BCG-vaccinated calves than in non-vaccinated calves. However, there was no statistically significant difference between the two groups (P > 0.05) in the response of CD68+ cells. Thus, the findings of this study indicated stronger responses of a set of immunological cells and markers at the local granulomas of BCG-vaccinated calves than in non-vaccinated calves. Furthermore, BCG vaccination may also play a role in reducing the severity of the gross pathology at the primary site of infection.

Tuberculosis Lymphadenitis and Human Immunodeficiency Virus Co-infections among Lymphadenitis Patients in Northwest Ethiopia.

BACKGROUND: Tuberculosis and human immunodeficiency virus (HIV) are among the major health problems in Ethiopia. This study assessed the proportion of tuberculosis lymphadenitis (TBLN), HIV infection and their co-infection among TBLN presumptive individuals at the selected hospitals in Northwest Ethiopia. METHODS: Institution based cross sectional study was carried out. Data on demographic and clinical variables were collected with standardized questionnaire. Microbiological culture was done on specimen obtained by fine needle aspirates. The HIV status was determined by rapid anti-HIV antibody test. Data was entered and scrutinized using SPSS version 20 statistical packages. A stepwise logistic regression model was used. The result was considered as statistically significant at P<0. 05. RESULTS: A total of 381 lymphadenitis patients were included in the study. The overall prevalence of TBLN and HIV were at 250(65.6%) and 9(2.4%), respectively and their co-infection was at 6(2.4%). Based on the cytological examination, 301(79.0%) of them were diagnosed as TBLN. The age group, (P=0.01) and residency, (P=0.01) were found significantly associated with TBLN. Similarly, unsafe sex was also statistically significant for HIV infection (P=0.007). CONCLUSION: Tuberculosis lymphadenitis is the leading cause of TB and lymphadenitis in the region. However, TBLN-HIV coinfection was promisingly low. High rate of discrepancy was noticed between cytological and culture results. Hence, the TBLN diagnostic criteria shall pursue revision.

Diabetes mellitus and HIV infection among active tuberculosis patients in Northwest Ethiopia: health facility-based cross-sectional study.

BACKGROUND: The prevalence of diabetes mellitus (DM) is increasing globally and its comorbidity with tuberculosis (TB) is re-emerging, especially in low- and middle-income countries. OBJECTIVE: The main aim of this study is to determine the prevalence of DM and HIV infection and their associated risk factors among active tuberculosis patients in Northwest Ethiopia. METHODS: This hospital-based cross-sectional study was conducted between February 1st and June 30th, 2017 among active TB patients in two hospitals of Northwest Ethiopia. Two hundred and sixty-seven active TB cases aged 18 years or older were screened for diabetes using fasting blood glucose (FBG) test. Semi-structured questionnaires were used to collect demographic data, lifestyle habits and clinical data. Identification of pre-diabetes or diabetes in TB patients was achieved according to American Diabetes Association guidelines (2016). RESULTS: Prevalence of DM and TB comorbidity was 11.5% (95% confidence interval, CI 7.8-15.2) compared to 24.9% (95% CI 20.1-30.1) for pre-diabetes. Prevalence of HIV/TB co-infection was 21.9% (95% CI 16.7-26.8). Risk of DM was higher in TB patients from a rural location (adjusted odds ratio, aOR 3.13, 95% CI 1.02-9.62, p = 0.046). Similarly, DM was higher in TB patients who have a family history of DM (aOR 4.54, 95% CI 1.31-15.68, p = 0.017). Furthermore, HIV/TB co-infection was identified as a predictor of DM comorbidity in active TB patients (aOR 5.11, 95% CI 2.01-12.98, p = 0.001). CONCLUSION: The magnitude of DM and pre-diabetes in active TB patients in Northwest Ethiopia was high, warranting collaborative efforts to improve screening and adopt better clinical management strategies for DM-TB comorbid patients. Furthermore, being rural residents, family history of DM and HIV/TB co-infection were found to associate with DM among TB patients, highlighting the importance of the above-mentioned risk factors in the clinical management of this comorbidity.