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Background: The burden of sepsis worsens due to the continuation of emerging pathogens such as multidrug-resistant Pantoea species. Methods: A multicenter study was conducted between October 2019 and September 2020 at four hospitals located in central, southern, and northern parts of Ethiopia. A total of 1416 sepsis patients were recruited and blood cultures were performed. At each study site, positive cultures were characterized by their colony characteristics, gram stain, and conventional biochemical tests. All Pantoea species were identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI TOF) and subjected to whole genome sequencing (WGS) using Illumina HiSeq 2500. The phylogeny structure of Pantoea isolates was calculated using IQ-TREE v1.6.12 from single-nucleotide polymorphisms detected by Snippy v.4.6.0 and filtered by Gubbins v.2.3.4. Average nucleotide identity was estimated by using OrthoANI v.0.93.1 on Shovill v.1.1.0 assemblies. Antimicrobial resistance genes and plasmid replicons were detected using ARIBA v.2.14.6. Phylogenetic trees were visualized using iTOLv.6.5.2. Results: Multiple Pantoea species include: P. dispersa (n = 19), P. septica (n = 1), and a novel Pantoea spp. (n = 1), were identified among sepsis patients. All P. dispersa isolates and the novel Pantoea species were isolated at Dessie Referral Hospital and displayed phylogenetic clonality, including the ubiquity of an IncM1 plasmid and identical antimicrobial resistance (AMR) gene profiles, encoding blaCTX−M−15, blaTEM−1D, blaSCO−1, and aac(3)-lla. The novel Pantoea spp. isolate harboured blaCTX−M−9 and blaTEM−1D and carried an IncN3 plasmid replicon. The P. septica was isolated at Tikur Anbessa Specialized Hospital in Addis Ababa and carried no detectable acquired AMR genes. Conclusion: The emerging Pantoea spp. carrying multiple AMR genes were identified from sepsis patients. Implementation of strong infection prevention strategies and building surveillance capacity with advanced bacteriology laboratories capable of identifying multidrug-resistant emerging pathogens is strongly recommended. [ABSTRACT FROM AUTHOR]

Background Loss to follow-up (LTFU) and death are unfavorable outcomes of human immunodeficiency virus (HIV) treatment. This study aimed to identify the predictors of LTFU and death among individuals with newly diagnosed HIV receiving dolutegravir (DTG)–based first-line antiretroviral treatment (ART) in eastern Ethiopia. Methods A multisite prospective cohort study was carried out between October 2020 and July 2022. New case patients who started ART were enrolled consecutively and then followed up for the next 6 months. A structured questionnaire and checklists were used to collect data. HIV viral load was determined using the Abbott RealTime HIV-1 assay. Bivariable and multivariable logistic regression models were used to identify baseline factors associated with the outcomes. Results A total of 235 people with newly diagnosed HIV were enrolled; 16.6% (95% confidence interval, 12.3%–21.9%) were lost to follow-up, and 5.9% (3.5%–9.8%) died within 6 months of follow-up. Baseline World Health Organization clinical stage I (adjusted odds ratio, 3.93 [95% confidence interval, 1.34–11.57]), low viral load (3.67 [1.09–12.36]), and body weight (1.04 [1.01–1.07]) were predictors of LTFU, whereas nonfunctional status (10.02 [1.9–51.3]) was the only factor associated with death. Conclusions LTFU and death rates among patients with DTG were relatively high, accounting for roughly a quarter of the attrition of people with newly diagnosed HIV from ART care and services. Thus, targeted interventions are required to reduce LTFU and death among individuals with HIV on ART. Further investigation is necessary to evaluate the long-term effects of DTG-based regimens on LTFU and its impact on HIV mortality rates, and qualitative research, specifically tracing LTFU, is recommended. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (bTB) is a disease with impact on dairy productivity, as well as having the potential for zoonotic transmission. Understanding the genetic diversity of the disease agent Mycobacterium bovis is important for identifying its routes of transmission. Here we investigated the level of genetic diversity of M. bovis isolates and assessed the zoonotic potential in risk groups of people working in bTB‐infected dairy farms in central Ethiopia. M. bovis was isolated and spoligotyped from tissue lesions collected from slaughtered cattle as well as from raw milk collected from bTB positive cows in dairy farms from six urban areas of central Ethiopia. From consented dairy farm workers, knowledge and practices related to zoonotic TB transmission, together with demographic and clinical information, was collected through interviews. Sputum or Fine Needle Aspirate (FNA) samples were collected from suspected TB cases. Spoligotyping of 55 M. bovis isolates that originated either from cattle tissues with tuberculous lesion or from raw milk revealed seven spoligotype patterns where SB1176 was the most prevalent type (47.3%). Most isolates (89.1%) were of the M. bovis African 2 clonal complex. All sputum and FNA samples from 41 dairy farm workers with symptoms of TB were culture negative for any mycobacteria. Among the 41 TB suspected farm workers, 61% did not know about bTB in cattle and its zoonotic potential, and over two‐third of these workers practiced raw milk consumption. Our spoligotype analysis suggests a wider transmission of a single spoligotype in the study area. The results reported here may be useful in guiding future work to identify the source and direction of bTB transmission and hence design of a control strategy. Isolation of M. bovis from milk, knowledge gap on zoonotic TB and practice of consumption of raw milk in the study population showed potential risk for zoonotic transmission. [ABSTRACT FROM AUTHOR]

Background: T cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB. Methodology: In this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa. Result: Levels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month. Conclusion: After six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is one of the major public health problems worldwide. Limited information exists about the epidemiology of HBV infection in Ethiopia. This study aimed to assess sero-prevalence of HBV markers and associated factors in children living in Hawassa City, southern Ethiopia.Methods: A community-based cross-sectional study was conducted among 471 children in Hawassa City, southern Ethiopia from May to September, 2018. A total of 471 children were included in the study using a multistage sampling technique. Data on demographic and risk factors were gathered using structured questionnaires. Blood samples were collected and sera were screened for hepatitis B surface antigen (HBsAg), antibody to core antigen (anti-HBc), and antibody against surface antigen (anti-HBs) using enzyme-linked immunosorbent assay.Results: The sero-prevalence of HBsAg, anti-HBc, and anti-HBs markers among children were 4.4, 19.5 and 20.0%, respectively. Children at higher risk of having HBsAg marker were those who had a history of injectable medications (AOR 5.02, 95% CI: 1.14, 22.07), a family history of liver disease (AOR 6.37, 95% CI: 1.32, 30.74), a HBsAg seropositive mothers, (AOR 11.19, (95% CI: 3.15, 39.67), and had no vaccination history for HBV (AOR, 6.37, 95% CI: 1.32, 30.74). Children from families with low monthly income, who were home delivered, unvaccinated for HBV or with HBsAg seropositive mother had increased risk of having anti-HBc.Conclusions: The study findings showed an intermediate endemicity of HBV infection in the study setting. The observed rate of residual HBV infection with low rate of immunized children after HBV vaccination was high. Hence, introducing birth dose vaccine, safe injection practice and improving immunization coverage during pregnancy as part of the antenatal care package should be considered. Furthermore, governmental and non-governmental organizations should give attention on timely measures for the prevention of ongoing vertical transmission from mother to child as well as early horizontal transmission of HBV in Hawassa City, Ethiopia. [ABSTRACT FROM AUTHOR]

Timely diagnosis of tuberculosis (TB) is limited in Ethiopia. We evaluated the performance of a low technology, thin layer agar, Mycobacterium tuberculosis (M.tb) culture color plate (TB-CX) test with concurrent drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) directly from sputum specimens. Patients undergoing examination for TB and multidrug-resistant (MDR)-TB were enrolled in Addis Ababa, Ethiopia from March 2016 to February 2017. All subjects received a GeneXpert MTB/RIF PCR test. TB-CX test results were compared to reference Löwenstein–Jensen (LJ) culture for M.tb detection and DST for susceptibility to INH and RIF. Kappa statistic was applied to test agreement between results for TB-CX test and the reference methods, a cut-off Kappa value of 0.75 was considered as high level of agreements. A total of 137 participants were analyzed: 88 (64%) were new TB cases, 49 (36%) were re-treatment cases. The TB-CX test detected M.tb and DST in an average of 13 days compared to 50 days for the conventional DST result. The sensitivity and specificity of the TB-CX test for detecting M.tb were 94% and 98%, respectively (concordance, 96%; kappa 0.91). The sensitivity of the TB-CX test to detect drug resistance to INH, RIF, and MDR-TB was 91%, 100%, and 90% respectively. The specificity of the TB-CX test for detecting INH, RIF, and MDR-TB was 94%, 40%, and 94% respectively. Overall agreement between TB-CX test and LJ DST for detection of MDR-TB was 93%. The TB-CX test showed strong agreement with the GeneXpert test for detecting M.tb (89%, kappa 0.76) but low agreement for the detection of RIF resistance (57%, kappa 0.28). The TB-CX test was found to be a good alternative method for screening of TB and selective drug resistant-TB in a timely and cost-efficient manner. [ABSTRACT FROM AUTHOR]

Background: Gut commensal bacteria can mediate resistance against pathogenic bacteria. However, exposure to antibiotics and hospitalization may facilitate the emergence of multidrug resistant bacteria. We aimed to conduct a systematic review and meta-analysis to provide comprehensive evidence about colonization rate of extended spectrum beta-lactamase and carbapenemases producing Enterobacteriaceae. Method: We used PubMed, Google Scholar and Web of Science data bases to search studies from January 1, 2016 to August10, 2022 about colonization rate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae. Data were extracted from eligible studies and analyzed using Stata version 16 software. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools, and publication bias was assessed using funnel plot and eggers test. Results: We identified 342 studies from the comprehensive data search and data were extracted from 20 studies. The pooled estimate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae were 45.6%(95%CI: 34.11-57-10) and 16.19% (95% CI: 5.46–26.91) respectively. The predominant extended spectrum beta-lactamase producers were E. coli,32.99% (95% CI: 23.28–42.69) and K. pneumoniae, 11.43% (95% CI:7.98–14.89). Prolonged hospitalization was linked to carbapenemase producing Enterobacteriaceae colonization with the odds of 14.77 (95% CI: -1.35–30.90) at admission and 45.63 (95% CI: 0.86–92.12) after ≥7 days of admission. Conclusion: The pooled estimate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae were high. This indicates the need for strong mitigation strategies to minimize the spread of multidrug-resistant bacteria at the healthcare facilities. [ABSTRACT FROM AUTHOR]

Background: In conjunction with the spread of HIV infection, tuberculosis (TB) remains a major cause of illness and death worldwide. The Ethiopian national report reveals that extra pulmonary tuberculosis is on the rise and that case detection rate is exceeding that of smear positive or negative cases in many parts of the country. Different studies indicated that host and/or pathogen related factors are associated with the rise of extra pulmonary cases. However, the reason for this is not clearly known in our setting.Methods: Specimens were taken from clinically suspected extra pulmonary patients and confirmed by cytology, histopathology and culture. Deletion typing and Spoligotyping was utilized to identify the strains. The isolates were then assigned to lineage using conformal Bayesian network (rules model) algorithm and dendrograms were drawn using UPGMA methods. In addition, drug sensitivity test was done using the indirect proportion and 24 well plate methods.Results: Out of the 200 clinically suspected extra pulmonary tuberculosis patients, 106 (53 %) were between 15 and 35 years of age and 167 (83.5 %) were new while 33 (16.5 %) were retreatment cases. The culture yield was 29.5 % (59). Of these only one was M. bovis and 58 were M. tuberculosis strains with 31 different spoligotype patterns grouped into seven clusters. The largest cluster (ST53) comprised 12 (20.3 %) isolates. There was higher clustering of CAS isolates in TBLN than in any other form of extra pulmonary tuberculosis cases. Resistance to rifampicin was higher (22 %) than that for INH, STM and EMB (8.1 %, 5 % and 3 % respectively). Out of the 37 isolates tested for resistance, only 2 isolates were resistant for both STM and INH and no MDR strain was found.Conclusions: There is an ongoing active recent transmission among extra pulmonary tuberculosis in the study areas as shown by the presence of clusters. Although no MDR case was observed, there is a risk of emergence of MDR as noted from the high proportion of resistance to rifampicin. Detailed study at population level is recommended to monitor its trend. [ABSTRACT FROM AUTHOR]

Dairy production is an important livelihood source for smallholder dairy farmers who produce the majority of milk consumed and traded in Ethiopia. Dairy production is, however, constrained by livestock diseases that impact farm productivity, food safety, and animal welfare. Biosecurity measures (BSM) include all risk reduction strategies designed to avoid the introduction of pathogenic infections from outside and minimise the spread of diseases within dairy herds. This study used a cross-sectional survey to investigate the adoption of BSM in dairy farms in Addis Ababa and Oromia regions of Ethiopia. Using a questionnaire, scores for adopted external and internal BSM were calculated based on the Ghent's University Biocheck tool to compare the performance of different farms in Ethiopia. The weighted external biosecurity score was 49.1%, which was below average (below 50% adoption), while the weighted internal biosecurity score was 55.5%. Low adoption of crucial BSM increases the risk of disease introduction into dairy farms and transmission within herds. Adoption of BSM at the farm level was driven by individual, demographic, and socio-economic drivers, including education, farming system, milk value chain, and farming experience among others. Results of this research reveal low adoption of BSM and the imperative to encourage farmers to implement BSM can lead to a reduction in disease pressures and, thus, a reduction in antibiotic use and increased dairy farms productivity, and improved animal health and welfare. Farmers can be encouraged through proactive engagement with veterinarians and extension professionals. Moreover, creating a favourable policy environment can support farmers to adopt and implement BSM, given the known fact that "prevention is better and cheaper than curing diseases." [ABSTRACT FROM AUTHOR]

Background Genetic factors are involved in susceptibility or protection to tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels of gene expression, induced by nongenetic factors, may also determine whether individuals progress to active TB. Methods We analysed the expression level of 45 genes in a total of 47 individuals (23 healthy household contacts and 24 new smear-positive pulmonary TB patients) in Addis Ababa using a dual colour multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess gene expression profiles that may be used to distinguish TB cases and their contacts and also latently infected (LTBI) and uninfected household contacts. Results The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO, MMP9, CCL19, and LTF had significant discriminatory power between sputum smear-positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79, 0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1, FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3 showed significant difference between LTBI and uninfected contacts, with AUCs of 0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3, FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts. Conclusions Expression of single and especially combinations of host genes can accurately differentiate between active TB cases and healthy individuals as well as between LTBI and uninfected contacts. [ABSTRACT FROM AUTHOR]

Background The immunologic environment during HIV/M. tuberculosis co-infection is characterized by cytokine and chemokine irregularities that have been shown to increase immune activation, viral replication, and T cell dysfunction. Methods We analysed ex vivo plasma samples from 17 HIV negative and 16 HIV pulmonary tuberculosis co infected cases using Luminex assay to see impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients before and after anti Tuberculosis treatment. Results The median plasma level of IFN-γ, IL-4, MCP-3, MIP-1β and IP-10 was significantly different (P < 0.05) before and after treatment in HIV negative TB patients but not in HIV positive TB patients. There was no significant difference between HIV positive and HIV negative TB patients (P > 0.05) in the plasma level of any of the cytokines or chemokines before treatment and anti TB treatment did not change the level of any of the measured cytokines in HIV positive tuberculosis patients. The ratio of IFN-γ/IL−10 and IFN-γ/IL−4 showed a significant increase after treatment in HIV negative TB cases but not in HIV positive TB cases which might indicate prolonged impairment of immune response to TB in HIV positive TB patients as compared to HIV negative tuberculosis patients. Conclusions HIV positive and HIV negative Tuberculosis patients display similar plasma cytokine and chemokine pattern. However, anti TB treatment significantly improves the Th1 cytokines and level of chemokines but does not restore the immune response in HIV positive individuals. [ABSTRACT FROM AUTHOR]

Background: Extrapulmonary tuberculosis (EPTB) constitutes about 10% to 20% of all cases of tuberculosis in immunocompetent patients and more than 50% of the cases in HIV-positive individuals worldwide. Little information is available on the clonal diversity of Mycobacterium species in Ethiopia from EPTB. Methods: This study was carried out on smear-negative EPTB patients to molecularly characterize Mycobacterium tuberculosis complex strains. A questionnaire, smear staining, culture, deletion typing, and spoligotyping were employed. Results: The proportional distribution of EPTB and isolates did not vary substantially ( p > 0.05) amongst the socio-demographic parameters considered in the current investigation. Out of 98 fine needle aspirates processed for culture, 36.7% (36/98) were positive for mycobacterial growth. Further speciation of those culture-positive isolates showed that 88.9% were M. tuberculosis and the remaining could be non-tuberculous mycobacterial species. Spoligotyping revealed 16 clusters out of which 2 were new to the SITVIT database. The most dominant spoligotypes were SIT54, SIT53, and SIT149 in decreasing order. SIT54, SIT134, SIT173, SIT345, SIT357, SIT926, SIT91088, and SIT1580 were reported for the first time in Ethiopia. The family with the highest frequency identified was M. tuberculosis family T1, followed by family 33. Most of the strains belonged to Euro-American (61.4%) and Indo-Oceanic (36.3%) lineages. Conclusions: The present study shows the importance of M. tuberculosis as a major cause of EPTB in the study area. Moreover, the majority of isolates of M. tuberculosis were found in clusters, suggesting the possibility of the existence of recent transmission. This warrants strengthening of the control programs for EPTB in the study area. [ABSTRACT FROM AUTHOR]

The immune response against Mycobacterium tuberculosis is multifactorial, involving a network of innate and adaptive immune responses. Characterization of the immune response, a clear understanding of the dynamics and interplay of different arms of the immune response are critical to allow the development of better tools for combating tuberculosis. Dendritic cells (DCs) are one of the key cells in bridging innate and adaptive immune response through their significant role in capturing, processing and presenting antigens. The outcome of interaction of M. tuberculosis with DCs is not fully understood and the available reports are contradictory were some findings reported that DCs strengthen the cellular immune response against mycobacterium infection whereas others reported M. tuberculosis impairs the function of DCs were infected DCs are poor stimulators of M. tuberculosis Agspecific CD4 T cells. Other studies showed that the outcome depends on M. tuberculosis strain type and type of receptor on DCs during recognition. In this review I shall highlight the recent findings in the outcome of interaction of Mycobacterium tuberculosis with DCs. [ABSTRACT FROM AUTHOR]

Epidemiological evidence from tuberculosis outbreaks revealed that some genotypes of M. tuberculosis are more transmissible and capable of causing disease than others. We analysed the plasma cytokine levels of pulmonary tuberculosis patients infected with different strains of M. tuberculosis to test the hypothesis that immune responses would be linked to the bacterial genotype. Spoligotyping was carried out for genotyping, and we used Luminex technology to measure 17 cytokines (EGF, fractalkine, GMCSF, IFN-γ, IL-1, IL-10, IL-12, IL-17, IL-4, IL-7, IL-9, IP-10, MCP-1, MCP-3, MIP-1β, TNF, and VEGF) from plasma samples of tuberculosis patients. The levels of IL-12 (p40), IL-4, IL-7, and MIP-1beta were higher in patients infected with lineage 3, however, it was only IL-4 which showed statistically significant difference (P < 0.05) between lineage 3 and lineage 4. We further grouped the lineages into families (CAS, H and T families), and we found that the plasma level of IL-4 was significantly higher in patients infected with the CAS family (P < 0.05) in comparison with T and H families. However, there was no difference between T and H families. Therefore, the higher level of IL-4 in lineage 3 families might indicate that possible differences in the response elicited from host depend on strain lineages in the studied population. [ABSTRACT FROM AUTHOR]

Understanding the genetic diversity of Mycobacterium tuberculosis is needed for a better understanding of the epidemiology of TB and could have implications for the development of new diagnostics, drugs, and vaccines. M. tuberculosis isolates were characterized using spoligotyping and were compared with the SpoIDB4 database of the Pasteur Institute of Guadeloupe. A total of 53 different patterns were identified among 192 isolates examined. 169 of the isolates were classified into one of the 33 shared SITs, whereas the remaining 23 corresponded to 20 orphan patterns. 54% of the isolates were ascribed to the T family, a family which has not been well defined to date. Other prominent families were CAS, Haarlem, LAM, Beijing, and Unknown comprising 26%, 13%, 2.6%, 0.5%, and 2.1%, respectively. Among HIV-positive patients, 10 patterns were observed among 25 isolates. The T (38.5%), H (26.9%), and CAS (23.1%) families were the most common among HIV-positive individuals. The diversity of the M. tuberculosis strains found in this study is very high, and there was no difference in the distribution of families in HIV-positive and HIV-negative TB patients except the H family. Tuberculosis transmission in Addis Ababa is due to only the modern M. tuberculosis families (CAS, LAM, T, Beijing, Haarlem, and U). [ABSTRACT FROM AUTHOR]

Background: Dendritic cells (DCs) can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood. Findings: To analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p < 0.05) up regulation following infection with M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS) from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation. Conclusion: These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro. [ABSTRACT FROM AUTHOR]

Background: Globally, extended-spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales are major causes of hospital-acquired infections and there are increasing concerns about their role in community-acquired infections. Objective: We aimed to investigate the prevalence of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and Carbapenemase-producing-Carbapenemresistant-Enterobacterales (CP-CRE) and associated factors in community settings in Gulele sub city, Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted among 261 healthy individuals. Stool samples were collected and processed using standard microbiological methods. Antimicrobial susceptibility and phenotypic ESBL and carbapenemase tests were performed. Antibiotic resistance genes were detected by Polymerase Chain Reaction (PCR). Results: The colonization rate of ESBL-PE and CP-CRE were 31.4% (82/261, 95% CI: 25.91–37.48) and 0.8% (2/261, 95% CI: 0.13–3.1), respectively by phenotypic method. Molecular detection of genes for ESBL-PE was 27.9% (73/261, 95% CI:22.7–33.9), and for CP-CRE was 0.8% (2/261, 95% CI: 0.13–3.1). The most prevalent genes were blaTEM [76.7% (56/73)] and blaCTX-M [45.2% (33/73)]. Previous antibiotic use (AOR:2.04, 95%CI: 1.35–4.41, P:0.041) and age between 42 and 53 years old (AOR:3.00, 95%CI:1.12–7.48, P:0.019) were significantly associated with ESBL-PE colonization. Conclusion: Intestinal colonization by ESBL-PE harboring the associated antibiotic resistance genes was substantially high but with low CP-CRE. Continued surveillance of community-level carriage of antimicrobial resistance Enterobacterales is warranted. [ABSTRACT FROM AUTHOR]

The diarrheagenic Escherichia coli (DEC) is the major cause of diarrheal diseases in Africa, including Ethiopia. However, the genetic diversity of E. coli pathotypes found in Ethiopia has not been studied well. This study aimed to characterize potential DEC belonging to enteropathogenic (EPEC), Shiga toxin-producing (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), and enteroinvasive (EIEC) E. coli pathotypes from stool specimens of patients attending primary healthcare units (n = 260) in Addis Ababa and Hossana using whole-genome sequencing. Real-time PCR assays were used to identify DEC isolates belonging to EPEC, STEC, EAEC, ETEC, and EIEC pathotypes, which were then subjected to whole-genome sequencing on the Illumina platform. Twenty-four whole-genome nucleotide sequences of DEC strains with good enough quality were analyzed for virulence-associated genes (VAGs), antibiotic resistance genes (ARGs), phylogenetic groups, serogroups, and sequence types. The majority (62.5%) of DEC isolates belonged to the phylogenetic group B1. The identified DEC isolates belonged to 21 different serogroups and 17 different sequence types. All tested DEC isolates carried multiple VAGs and ARGs. The findings highlight the high diversity in the population structure of the studied DEC isolates, which is important for designing targeted interventions to reduce the diarrheal burden in Ethiopia. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae, a medically important opportunistic bacterial pathogen of the upper respiratory tract, is a major public health concern, causing a wide range of pneumococcal illnesses, both invasive and noninvasive. It is associated with significant global morbidity and mortality, including pneumonia, meningitis, sepsis, and acute otitis media. The major purpose of this study was to determine the molecular epidemiology of Streptococcus pneumoniae strains that cause invasive and noninvasive infections in Ethiopia. A prospective study was undertaken in two regional hospitals between January 2018 and December 2019. Whole-genome sequencing was used to analyze all isolates. Serotypes and multilocus sequence types (MLST) were derived from genomic data. The E-test was used for antimicrobial susceptibility testing. Patient samples obtained 54 Streptococcus pneumoniae isolates, 33 from invasive and 21 from noninvasive specimens. Our findings identified 32 serotypes expressed by 25 Global Pneumococcal Sequence Clusters (GPSCs) and 42 sequence types (STs), including 21 new STs. The most common sequence types among the invasive isolates were ST3500, ST5368, ST11162, ST15425, ST15555, ST15559, and ST15561 (2/33, 6% each). These sequence types were linked to serotypes 8, 7 C, 15B/C, 16 F, 10 A, 15B, and 6 A, respectively. Among the noninvasive isolates, only ST15432, associated with serotype 23 A, had numerous isolates (4/21, 19%). Serotype 14 was revealed as the most resistant strain to penicillin G, whereas isolates from serotypes 3, 8, 7 C, and 10 A were resistant to erythromycin. Notably, all serotype 6 A isolates were resistant to both erythromycin and penicillin G. Our findings revealed an abnormally significant number of novel STs, as well as extremely diversified serotypes and sequence types, implying that Ethiopia may serve as a breeding ground for novel STs. Recombination can produce novel STs that cause capsular switching. This has the potential to influence how immunization campaigns affect the burden of invasive pneumococcal illness. The findings highlight the importance of continuous genetic surveillance of the pneumococcal population as a vital step toward enhancing future vaccine design. [ABSTRACT FROM AUTHOR]

Despite recent improvements in microbial detection, smear-negative TB remains a diagnostic challenge. In this study, we investigated the potential discriminatory role of polychromatic flow cytometry of M. tuberculosis antigen-specific T cells to discriminate smear-negative TB from health controls with or without latent TB infection, and non-TB respiratory illnesses in an endemic setting. A cross-sectional study was conducted on HIV negative, newly diagnosed smear-positive PTB (n = 34), smear-negative/GeneXpert negative PTB (n = 29) patients, non-TB patients with respiratory illness (n = 33) and apparently healthy latent TB infected (n = 30) or non-infected (n = 23) individuals. The expression of activation (HLA-DR, CD-38), proliferation (Ki-67), and functional (IFN-γ, TNF-α) T-cell markers using polychromatic flow cytometry was defined after stimulation with PPD antigens. Sputum samples were collected and processed from all patients for Mtb detection using a concentrated microscopy, LJ/MGIT culture, and RD9 typing by PCR. Our study showed CD4 T cells specific for PPD co-expressed activation/proliferation markers together with induced cytokines IFN-γ or TNF-α were present at substantially higher levels among patients with smear-positive and smear-negative pulmonary TB than among healthy controls and to a lesser extent among patients with non-TB illness. Our study conclude that smear-negative TB can be distinguished from non-TB respiratory illness and healthy controls with a flow cytometric assay for PPD-specific T cells co-expressing activation/proliferation markers and cytokines. Substantially high level of activation markers was observed among smear positive pulmonary TB patients. Flow cytometry could be a potential tool to distinguish smear negative pulmonary TB from healthy control and non TB respiratory illness. [ABSTRACT FROM AUTHOR]

The diagnosis and prognosis of tuberculosis remains challenging and necessitates the development of a new test that can accurately diagnose and monitor treatment responses. In this regard, miRNA is becoming a potential diagnostic and prognostic biomarker which differentiates treatment respondents from non-respondents for various non-infectious and infectious diseases, including tuberculosis. The concentration of miRNAs varies based on cell type, disease, and site of infection, implicating that selection of an optimal reference gene is crucial, and determines the quantification of transcript level and biological interpretation of the data. Thus, the study evaluated the stability and expression level of five candidate miRNAs (let-7i-5p, let-7a-5p, miRNA-16-5p, miRNA-22-3p and miRNA-93-5p), including U6 Small Nuclear RNA (RNU6B) to normalize circulating miRNAs in the plasma of 68 participants (26 healthy controls, 23 latent, and 19 pulmonary tuberculosis infected) recruited from four health centers and three hospitals in Addis Ababa, Ethiopia. The expression levels of miRNAs isolated from plasma of culture confirmed newly diagnosed pulmonary tuberculosis patients were compared with latently infected and non-infected healthy controls. The qPCR data were analyzed using four independent statistical tools: Best Keeper, Genorm, Normfinder and comparative delta-Ct methods, and the data showed that miRNA-22-3p and miRNA-93-5p were suitable plasma reference miRNAs in a tuberculosis study. [ABSTRACT FROM AUTHOR]

Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s). [ABSTRACT FROM AUTHOR]

We determined the dengue virus (DENV) serotypes and genotypes in archived serum samples that were collected during the 2014–2016 and 2021 dengue outbreaks in Dire Dawa City and the Somali region in Ethiopia. DENV serotype 1 (DENV-1) was predominant followed by DENV serotype 2 (DENV-2). Thirteen of the DENV-1 strains were assigned to Genotype-I, while the remaining two were found to be Genotype-III. All three DENV-2 strains were assigned the Cosmopolitan Genotype. The DENV strains responsible for the outbreaks are genetically closely related to the DENV strains that circulated in neighboring and Asian countries. The findings also showed continued local transmission of a monophyletic lineage and a co-circulation of DENV-1 and DENV-2 during the outbreaks. There is a need to strengthen DENV genomic surveillance capacity for the early detection of circulating serotypes, and prevent devastating consequences of future outbreaks due to the co-circulation of different serotypes. [ABSTRACT FROM AUTHOR]

Background: Cholera is an acute infectious disease caused by ingestion of contaminated food or water with Vibrio cholerae. Cholera remains a global threat to public health and an indicator of inequity and lack of social development. The aim of this study was to assess the prevalence and antimicrobial susceptibility pattern of V. cholerae from cholera outbreak sites in Ethiopia. Methods: Across-sectional study was conducted from May 2022 to October 2023 across different regions in Ethiopia: Oromia National Regional State, Amhara National Regional State and Addis Ababa City Administration. A total of 415 fecal samples were collected from the three regions. Two milliliter fecal samples were collected from each study participants. The collected samples were cultured on Blood Agar, MacConkey Agar and Thiosulfate Citrate Bile Salt Sucrose Agar. A series of biochemical tests Oxidase test, String test, Motility, Indole, Citrate, Gas production, H2S production, Urease test were used to identify V. cholerae species. Both polyvalent and monovalent antisera were used for agglutination tests to identify and differentiate V. cholerae serogroup and serotypes. In addition, Kirby-Bauer Disk diffusion antibiotic susceptibility test method was done. Data were registered in epi-enfo version 7 and analyzed by Statistical Package for Social Science version 25. Descriptive statistics were used to determine the prevalence of Vibrio cholerae. Logistic regression model was fitted and p-value < 0.05 was considered as statically significant. Results: The prevalence of V. cholerae in the fecal samples was 30.1%. Majority of the isolates were from Oromia National Regional State 43.2% (n = 54) followed by Amhara National Regional State 31.2% (n = 39) and Addis Ababa City Administration 25.6% (n = 32). Most of the V. cholerae isolates were O1 serogroups 90.4% (n = 113) and Ogawa serotypes 86.4% (n = 108). Majority of the isolates were susceptible to ciprofloxacin 100% (n = 125), tetracycline 72% (n = 90) and gentamycin 68% (n = 85). More than half of the isolates were resistant to trimethoprim-sulfamethoxazole 62.4% (n = 78) and ampicillin 56.8% (n = 71). In this study, participants unable to read and write were about four times more at risk for V. cholerae infection (AOR: 3.8, 95% CI: 1.07–13.33). In addition, consumption of river water were about three times more at risk for V. cholerae infection (AOR: 2.8, 95% CI: 1.08–7.08). Conclusion: our study revealed a high prevalence of V. cholerae from fecal samples. The predominant serogroups and serotypes were O1 and Ogawa, respectively. Fortunately, the isolates showed susceptible to most tested antibiotics. Drinking water from river were the identified associated risk factor for V. cholerae infection. Protecting the community from drinking of river water and provision of safe and treated water could reduce cholera outbreaks in the study areas. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a chronic communicable bacterial disease caused by Mycobacterium tuberculosis complex (MTBC) species. M. tuberculosis is the main causative agent of human TB, and cattle are the primary host of Mycobacterium bovis; due to close interaction between cattle and humans, M. bovis poses a zoonotic risk. This review summarizes and estimates the prevalence of M. bovis infection among human cases. Studies reporting TB prevalence data that were published in English during 10 years from 20 April 2009 to 17 April 2019 were identified through search of PubMed and other sources. Quality of studies and risk of bias were assessed using standard tools for prevalence study reports. Characteristics of included studies and their main findings were summarized in tables and discussed with narrative syntheses. Meta‐analysis was performed on 19 included studies, with a total of 7,185 MTBC isolates identified; 702 (9.7%) of them were characterized as of subspecies M. bovis, but there was a large prevalence difference between the studies, ranging from 0.4% to 76.7%. The genotyping‐based studies reported significantly lower prevalence of zoonotic TB than did the studies based on older techniques. The overall pooled prevalence of M. bovis aggregated from all included studies was 12.1% of the total MTBC isolates, while the corresponding pooled figure from the 14 genotyping‐based studies was only 1.4%. Generally, human M. bovis cases reported from different countries of the world suggest that the impact of zoonotic TB is still important in all regions. However, it was difficult to understand the true picture of the disease prevalence because of methodological differences. Future investigations on zoonotic TB should carefully consider these differences when evaluating prevalence results. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb), the main etiology of tuberculosis (TB), is predominantly an intracellular pathogen that has caused infection, disease and death in humans for centuries. Lipid droplets (LDs) are dynamic intracellular organelles that are found across the evolutionary tree of life. This review is an evaluation of the current state of knowledge regarding Mtb-LD formation and associated Mtb transcriptome directly from sputa. Based on the LD content, Mtb in sputum may be classified into three groups: LD positive, LD negative and LD borderline. However, the clinical and evolutionary importance of each state is not well elaborated. Mounting evidence supports the view that the presence of LD positive Mtb bacilli in sputum is a biomarker of slow growth, low energy state, towards lipid degradation, and drug tolerance. In Mtb, LD may serve as a source of chemical energy, scavenger of toxic compounds, prevent destruction of Mtb through autophagy, delay trafficking of lysosomes towards the phagosome, and contribute to Mtb persistence. It is suggest that LD is a key player in the induction of a spectrum of phenotypic and metabolic states of Mtb in the macrophage, granuloma and extracellular sputum microenvironment. Tuberculosis patients with high proportion of LD positive Mtb in pretreatment sputum was associated with higher rate of poor treatment outcome, indicating that LD may have a clinical application in predicting treatment outcome. The propensity for LD formation among Mtb lineages is largely unknown. The role of LD on Mtb transmission and disease phenotype (pulmonary TB vs extra-pulmonary TB) is not well understood. Thus, further studies are needed to understand the relationships between LD positivity and Mtb lineage, Mtb transmission and clinical types. [ABSTRACT FROM AUTHOR]

Background: Previous work has shown differential predominance of certain Mycobacterium tuberculosis (M. tb) lineages and sub-lineages among different human populations in diverse geographic regions of Ethiopia. Nevertheless, how strain diversity is evolving under the ongoing rapid socio-economic and environmental changes is poorly understood. The present study investigated factors associated with M. tb lineage predominance and rate of strain clustering within urban and peri-urban settings in Ethiopia. Methods: Pulmonary Tuberculosis (PTB) and Cervical tuberculous lymphadenitis (TBLN) patients who visited selected health facilities were recruited in the years of 2016 and 2017. A total of 258 M. tb isolates identified from 163 sputa and 95 fine-needle aspirates (FNA) were characterized by spoligotyping and compared with international M.tb spoligotyping patterns registered at the SITVIT2 databases. The molecular data were linked with clinical and demographic data of the patients for further statistical analysis. Results: From a total of 258 M. tb isolates, 84 distinct spoligotype patterns that included 58 known Shared International Type (SIT) patterns and 26 new or orphan patterns were identified. The majority of strains belonged to two major M. tb lineages, L3 (35.7%) and L4 (61.6%). The observed high percentage of isolates with shared patterns (n = 200/258) suggested a substantial rate of overall clustering (77.5%). After adjusting for the effect of geographical variations, clustering rate was significantly lower among individuals co-infected with HIV and other concomitant chronic disease. Compared to L4, the adjusted odds ratio and 95% confidence interval (AOR; 95% CI) indicated that infections with L3 M. tb strains were more likely to be associated with TBLN [3.47 (1.45, 8.29)] and TB-HIV co-infection [2.84 (1.61, 5.55)]. Conclusion: Despite the observed difference in strain diversity and geographical distribution of M. tb lineages, compared to earlier studies in Ethiopia, the overall rate of strain clustering suggests higher transmission and warrant more detailed investigations into the molecular epidemiology of TB and related factors. [ABSTRACT FROM AUTHOR]

Introduction: The treatment response of multi-drug resistance tuberculosis (MDR-Tuberculosis) patients is mainly dictated by the sputum culture conversion. An earlier culture conversion is a remarkable indicator of the improvement in the treatment response. In this study, we aimed to determine the time to culture conversion and its associated factors among MDR-Tuberculosis patients in All Africa Leprosy, Tuberculosis and Rehabilitation Training Center (ALERT) Hospital, Addis Ababa, Ethiopia. Methods: A retrospective cohort study was conducted on 120 MDR-Tuberculosis patients attending ALERT Hospital from 2018–2022. Kaplan-Meier methods were used to determine the time to initial sputum culture conversion. All relevant laboratory, socio-demographic characteristics, and other clinical data were collected by chart abstraction using a structure data extraction form. The log-rank test was used to determine the survival rate. To identify the predictors of culture conversion, bivariate and multivariate Cox proportional hazard regression analysis was used. The hazard ratio (HR) with a 95% confidence interval was used to estimate the effect of each variable on the initial culture conversion. A test with a P value of < 0.05 was considered statistically significant. Results: From the total of 120 study participants, 89.2% (107/120) have shown a successful culture conversion. The median age of the participants was 30 years (IQR = 12). The study participants were followed for 408.6 person-months (34.05 person-years). The median time to initial sputum culture conversion was 80 days. The median time to initial sputum culture conversion among HIV-positive and HIV-negative participants was 61 days (IQR = 58–63.5) and 88 days (IQR = 75–91), respectively. HIV-negative and patients with previous treatment history were shown to be the predictor for a prolonged time to initial sputum culture conversion, (aHR = 0.24 (95% CI: 0.1–0.4), P value <0.001) and (aHR = 0.47 (95% CI: 0.31–0.71), P value <0.001) respectively. Conclusion: The median time to sputum culture conversion for HIV positive was found to be 61 days in our study. Notably, patients with a history of previous anti-tuberculosis treatment, HIV-negative status, and higher bacillary load at baseline exhibited delayed culture conversion. These findings underscore the importance of considering such patient characteristics in the management of MDR-TB cases, as tailored interventions and close monitoring may lead to more favorable treatment outcomes. By identifying individuals with these risk factors early in the treatment process, healthcare providers can implement targeted strategies to optimize patient care and improve overall treatment success rates in MDR-TB management programs. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii is an opportunistic pathogen that can cause a variety of nosocomial infections in humans. This study aimed to molecularly characterize extended-spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Acinetobacter species isolated from surgical site infections (SSI). Methods: A multicentre cross-sectional study was performed among SSI patients at four hospitals located in Northern, Southern, Southwest, and Central parts of Ethiopia. The isolates were identified by microbiological methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility was determined using disk diffusion. The presence of phenotypic ESBL and carbapenemase production was detected by employing standard microbiological tests, including combined disk diffusion (CDT). ESBL and carbapenem resistance determinants genes were studied by polymerase chain reaction (PCR) and sequencing. Results: A total of 8.7% Acinetobacter species were identified from 493 culture-positive isolates out of 752 SSI wounds. The species identified by MALDI-TOF MS were 88.4% A. baumannii, 4.7% Acinetobacter pittii, 4.7% Acinetobacter soli, and 2.3% Acinetobacter lactucae. Of all isolates 93% were positive for ESBL enzymes according to the CDT. Using whole genome sequencing 62.8% of the A. baumannii harbored one or more beta-lactamase genes, and 46.5% harbored one or more carbapenemase producing genes. The distribution of beta-lactamases among Acinetobacter species by hospitals was 53.8%, 64.3%, 75%, and 75% at JUSH, TASH, DTCSH, and HUCSH respectively. Among ESBL genes, blaCTX−M alleles were detected in 21.4% of isolates; of these 83.3% were blaCTX−M−15. The predominant carbapenemase gene of blaOXA type was detected in 24 carbapenem-resistant A. baumannii followed by blaNDM alleles carried in 12 A. baumannii with blaNDM−1 as the most common. Conclusions: The frequency of Acinetobacter species that produce metallobetalactamases (MBLs) and ESBLs that were found in this study is extremely scary and calls for strict infection prevention and control procedures in health facilities helps to set effective antibiotics stewardship. [ABSTRACT FROM AUTHOR]

Cervical cancer is a significant public health concern in Ethiopia. It is mainly caused by persistent infection with the human papillomaviruses. The aim of this study was to assess the relationship between carcinogenic risk of probable, possible and low risk HPV infection and those of cervical intraepithelial neoplasia (CIN) and cervical cancer. A cross sectional study nested from prospective cohort study was conducted in Bahir Dar, northwest Ethiopia. Statistical analyses were performed using SPSSversion 26.0. HPV-16 was associated with a relatively higher risk of CIN II+, (AOR = 15.42; 95% CI 6.81–34.91). In addition, HPV-52, -18, -53 and -58, were significantly associated with an increased risk of CIN II+, (AOR = 7.38 (1.73–31.54), 5.42 (1.61–18.31), 4.08 (1.53–10.87), and 3.17 (1.00–10.03)), respectively. The current study shows high rate of HPV with predominance of HPV-16, -53, -58, -18, -35, and -52. The quadrivalent and nonavalent vaccine had only covered 27.1% and 45% of the circulating HPV genotypes. Ethiopia may need to consider introduction of nonavalent vaccine into the national public health strategy. Polyvalent vaccine which includes the genotypes not covered by existing approved vaccines should be considered. [ABSTRACT FROM AUTHOR]

A comprehensive understanding of the dynamics of Streptococcus pneumoniae colonization in conjunction with respiratory virus infections is essential for enhancing our knowledge of the pathogenesis and advancing the development of effective preventive strategies. Therefore, a case–control study was carried out in Addis Ababa, Ethiopia to investigate the colonization rate of S. pneumoniae and its coinfection dynamics with respiratory viruses among children under the age of 5 years. Samples from the nasopharyngeal and/or oropharyngeal, along with socio-demographic and clinical information, were collected from 420 children under 5 years old (210 cases with lower respiratory tract infections and 210 controls with conditions other than respiratory infections.). A one-step Multiplex real-time PCR using the Allplex Respiratory Panel Assays 1–4 was performed to identify respiratory viruses and bacteria. Data analysis was conducted using STATA software version 17. The overall colonization rate of S. pneumoniae in children aged less than 5 years was 51.2% (215/420). The colonization rates in cases and controls were 54.8% (115/210) and 47.6% (100/210), respectively (p = 0.14). Colonization rates were observed to commence at an early age in children, with a colonization rate of 48.9% and 52.7% among infants younger than 6 months controls and cases, respectively. The prevalence of AdV (OR, 3.11; 95% CI [1.31–8.19]), RSV B (OR, 2.53; 95% CI [1.01–6.78]) and HRV (OR, 1.7; 95% CI [1.04–2.78]) tends to be higher in children who tested positive for S. pneumoniae compared to those who tested negative for S. pneumoniae. Further longitudinal research is needed to understand and determine interaction mechanisms between pneumococci and viral pathogens and the clinical implications of this coinfection dynamics. [ABSTRACT FROM AUTHOR]

Bartonella quintana is a louse-borne gram-negative bacillus that remains a poorly characterized cause of bacteremia, fever, and infective endocarditis. Due to the link with pediculosis, B quintana transmission is tied to poverty, conflict, overcrowding, and inadequate water access to maintain personal hygiene. Although these risk factors may be present globally, we argue that a substantial burden of undocumented B quintana infection occurs in Africa due to the high prevalence of these risk factors. Here, we describe the neglected burden of B quintana infection, endocarditis, and vector positivity in Africa and evaluate whether B quintana meets criteria to be considered a neglected tropical disease according to the World Health Organization. [ABSTRACT FROM AUTHOR]

The World Health Organization [WHO] recommends a genotype-specific human papillomavirus [HPV] vaccination as a primary prevention strategy to control the burden of cervical cancer globally. In Ethiopia, where the non-vaccine-targeted HPV genotypes have not been adequately studied, a vaccination initiative was launched in 2018 targeting HPV-6,-11, -16, and -18 for girls aged 14–18 years. The co-existence of both vaccine-targeted and non-targeted genotypes is a serious concern, as it can accelerate cancer progression. Therefore, this study was conducted to determine the prevalence of non-vaccine-targeted HPV genotypes and assess the level of multiple infections with other genotypes in eastern Ethiopia. A health facility-based cross-sectional study including 110 women with positive HPV DNA results was conducted from April to August 2021. A structured questionnaire to collect demographic and clinical data was used. Cervical swabs were collected using L-shaped FLOQSwabs. Women's cytological profile was determined based on Pap smear test results. An automated nucleic acid extraction system using STARMag 96 ProPrep Universal Extraction Kit was utilized following the manufacturer's protocol. An amplification assay in real-time was employed to amplify and identify the HPV Late 1 [L1] gene, which is utilized for genotyping purposes. Following this, the collected data was entered into Epi data version 3.1 software, and the analysis was performed using STATA version 14. A total of 110 women [age range 30–60 years, mean age = 36.5 years and SD ± 6.9] had positive HPV DNA results and were included in the study. Among these, 108 women had valid co-testing [Pap test and HPV DNA test] results for further analysis, and the results of the remaining 2 women were rejected. Overall, the prevalence of non-vaccine-targeted HPV was 56 (51.8%, 95%CI [0.42, 0.61]), of which 28 women (25.4%, 95%CI [0.18, 0.34]) had a single non-vaccine HPV genotype infection. The remaining 29 women (26.4%, 95% CI: 0.190–0.355) experienced multiple infections. The non-vaccine-targeted genotypes of HPV-35 accounted for 11 cases (10%, 95%CI [0.06, 0.17]), HPV-68 was detected in 9 women (8.2%, 95%CI [0.04, 0.15]), HPV-56 and HPV-66 were both found in 8 cases each (7.3%, 95%CI [0.04, 0.14]) of the total. In addition, out of these 108 women, 93 (86.1%, 95%CI [0.78, 0.91]) had low-grade squamous intraepithelial lesions, 13 (12%, 95%CI [0.07, 0.20]) no intraepithelial lesion or malignancy, and two (1.9%, 95%CI [0.01, 0.07]) high-grade squamous intraepithelial lesions. Furthermore, there was no statistical difference [p = 0.755] between vaccine-targeted and non-vaccine-targeted genotypes as the primary cause of cervical lesions. In conclusion, the findings of the present study highlight the existence of a notable prevalence of multiple infections caused by non-vaccine-targeted HPV genotypes. Therefore, it is recommended that both the Federal and regional health bureaus to evaluate the range of hr HPV genotypes protected by the current HPV vaccine and explore the option of transitioning from the quadrivalent HPV vaccine to a novavalent vaccine that includes seven high-risk HPV genotypes. [ABSTRACT FROM AUTHOR]

Background: Genetic factors are involved in susceptibility or protection to tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels of gene expression, induced by non-genetic factors, may also determine whether individuals progress to active TB.Methods: We analysed the expression level of 45 genes in a total of 47 individuals (23 healthy household contacts and 24 new smear-positive pulmonary TB patients) in Addis Ababa using a dual colour multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess gene expression profiles that may be used to distinguish TB cases and their contacts and also latently infected (LTBI) and uninfected household contacts.Results: The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO, MMP9, CCL19, and LTF had significant discriminatory power between sputum smear-positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79, 0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1, FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3 showed significant difference between LTBI and uninfected contacts, with AUCs of 0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3, FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts.Conclusions: Expression of single and especially combinations of host genes can accurately differentiate between active TB cases and healthy individuals as well as between LTBI and uninfected contacts. [ABSTRACT FROM AUTHOR]

Background: The immunologic environment during HIV/M. tuberculosis co-infection is characterized by cytokine and chemokine irregularities that have been shown to increase immune activation, viral replication, and T cell dysfunction.Methods: We analysed ex vivo plasma samples from 17 HIV negative and 16 HIV pulmonary tuberculosis co infected cases using Luminex assay to see impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients before and after anti Tuberculosis treatment.Results: The median plasma level of IFN-γ, IL-4, MCP-3, MIP-1β and IP-10 was significantly different (P < 0.05) before and after treatment in HIV negative TB patients but not in HIV positive TB patients. There was no significant difference between HIV positive and HIV negative TB patients (P > 0.05) in the plasma level of any of the cytokines or chemokines before treatment and anti TB treatment did not change the level of any of the measured cytokines in HIV positive tuberculosis patients. The ratio of IFN-γ/IL-10 and IFN-γ/IL-4 showed a significant increase after treatment in HIV negative TB cases but not in HIV positive TB cases which might indicate prolonged impairment of immune response to TB in HIV positive TB patients as compared to HIV negative tuberculosis patients.Conclusions: HIV positive and HIV negative Tuberculosis patients display similar plasma cytokine and chemokine pattern. However, anti TB treatment significantly improves the Th1 cytokines and level of chemokines but does not restore the immune response in HIV positive individuals. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infections (LRTIs) are a major cause of morbidity and mortality in children worldwide and disproportionally affect Sub-Saharan Africa. Despite the heaviest burden of LRIs in Ethiopia, to date, no published studies have reported a comprehensive viral etiology of LRTIs among children in Ethiopia. The objective of this study was to determine and estimate the etiological contribution of respiratory viruses to LRTIs in < 5 years children in Ethiopia. Methods: A prospective case–control study was conducted from September 2019 to May 2022 in two major governmental hospitals, St. Paul Hospital Millennium Medical College and ALERT Hospital in Addis Ababa, Ethiopia. Nasopharyngeal/oropharyngeal samples and socio-demographic and clinical information were collected from children under 5 years. A one-step Multiplex real-time PCR (Allplex™ Respiratory Panel Assays 1–3) was done to detect respiratory viruses. STATA software version 17 was used for the data analysis. We computed the odds ratio (OR), the attributable fraction among exposed (AFE) and the population attributable fraction (PAF) to measure the association of the detected viruses with LRTIs. Results: Overall, 210 LRTIs cases and 210 non-LRTI controls were included in the study. The likelihood of detecting one or more viruses from NP/OP was higher among cases than controls (83.8% vs. 50.3%, p = 0.004). The multivariate logistic regression showed a significantly higher detection rate for RSV A (OR: 14.6, 95% CI 4.1–52.3), RSV B (OR: 8.1, 95% CI 2.3–29.1), influenza A virus (OR: 5.8, 95% CI 1.5–22.9), and PIV 1 (OR: 4.3, 95% CI 1.1–16.4), among cases when compared with controls. The overall AFE and PAF for RSV A were (93.2% and 17.3%), RSV B (87.7% and 10.4%) and Influenza A virus (82.8% and 6.3%), respectively. The mean CT values were significantly lower for only RSV B detected in the case groups as compared with the mean CT values of RSV B detected in the control group (p = 0.01). Conclusions: RSV, Influenza A and PIV 1 viruses were significantly associated with LRTIs in < 5 years children in Addis Ababa, Ethiopia. Therefore, we underscore the importance of developing prevention strategies for these viruses in Ethiopia and support the importance of developing and introducing an effective vaccine against these viruses. [ABSTRACT FROM AUTHOR]

Background: Diarrhea is a serious health problem in children, with the highest mortality rate in sub-Saharan Africa. Diarrheagenic Escherichia coli (DEC) is among the major bacterial causes of diarrhea in children under age five. The present study aims to determine molecular epidemiology and antimicrobial resistance profiles of DEC and identify contributing factors for acquisition among children under age five in Central Ethiopia. Methods: A health facility-centered cross-sectional study was conducted in Addis Ababa and Debre Berhan, Ethiopia, from December 2020 to August 2021. A total of 476 specimens, 391 from diarrheic and 85 from non-diarrheic children under age five were collected. Bacterial isolation and identification, antimicrobial susceptibility, and pathotype determination using polymerase chain reaction (PCR) were done. Results: Of the 476 specimens analyzed, 89.9% (428/476) were positive for E. coli, of which 183 were positive for one or more genes coding DEC pathotypes. The overall prevalence of the DEC pathotype was 38.2% (183/476). The predominant DEC pathotype was enteroaggregative E. coli (EAEC) (41.5%, 76/183), followed by enterotoxigenic E. coli (21.3%, 39/183), enteropathogenic E. coli (15.3%, 28/183), enteroinvasive E. coli (12.6%, 23/183), hybrid strains (7.1%, 13/183), Shiga toxin-producing E. coli (1.6%, 3/183), and diffusely-adherent E. coli (0.6%, 1/183). DEC was detected in 40.7% (159/391) of diarrheic and 28.2% (24/85) in non-diarrheic children (p = 0.020). The majority of the DEC pathotypes were resistant to ampicillin (95.1%, 174/183) and tetracycline (91.3%, 167/183). A higher rate of resistance to trimethoprim-sulfamethoxazole (58%, 44/76), ciprofloxacin (22%, 17/76), ceftazidime and cefotaxime (20%, 15/76) was seen among EAEC pathotypes. Multidrug resistance (MDR) was detected in 43.2% (79/183) of the pathotypes, whereas extended spectrum ß-lactamase and carbapenemase producers were 16.4% (30/183) and 2.2% (4/183), respectively. Conclusion: All six common DEC pathotypes that have the potential to cause severe diarrheal outbreaks were found in children in the study area; the dominant one being EAEC with a high rate of MDR. [ABSTRACT FROM AUTHOR]

Background: Leukemic patients are prone to infectious agents such as viruses due to dysregulated immune system resulting from infiltration of the bone marrow by malignant cells, chronic stimulation, reactivation of some viruses and viral pathogenicity as well as rarely from acquisition of a new infections leading to severe complications. However, the prevalence of these infections has not been systematically documented in resource-limited settings such as Ethiopia. Objective: To determine the prevalence of HBV, HCV, and HIV among adult and adolescent in-patients with acute leukemia before the administration of chemotherapy, at the Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. Methods: A cross sectional study was conducted on 176 adult and adolescent inpatient Ethiopians, who were diagnosed with acute leukemia from April 2019 to June 2021. Socio-demographic characteristics and relevant clinical data were collected. Peripheral blood samples were collected and tested for HBV, HIV, and HCV using Enzyme-Linked Immunosorbent Assay (ELISA) and real-time PCR. Chi-square tests were used to assess associations between variables. Results: Of the 176 patients, 109(62%) were males. The median age was 25[IQR,18–35] yr, with a range from 13 to 76 year. The prevalence of HBV (positivity for HBsAg plus HBV DNA), HCV and HIV was 21.6%, 1.7%, and 1.7%, respectively. HBsAg was positive in 19 cases (10.8%). Among 157 HBsAg negative patients, 52(33.1%) were positive for Anti-HBcAg; of these seropositive cases, 47.5% were positive for HBV DNA. Most DNA positive, HBsAg negative cases (79.0%) had DNA concentrations below 200 IU/ml indicating true occult HBV infection (OBI). Of the 176 cases, 122 had a history of blood transfusions, but no statistically significant association was found between HBV infection and blood product transfusion history (P = 0.963). Conclusions: The prevalence of HBV, HIV and HCV in patients with acute leukemia was similar to the national prevalence level of these infections. Given the HBsAg positivity and the high prevalence of occult hepatitis B infection in our study, these patients may be at increased risk for chemotherapy related hepatitis flares. Hence, clinicians caring these patients are strongly advised to screen their patients for HBV and also for HIV and HCV infections routinely. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B vaccination is recommended for all children at birth within 24 hours or during childhood. Objective: This study was aimed to evaluate protective efficacy of hepatitis B vaccine and estimate the sero-prevalence of hepatitis B virus infection among vaccinated children. Materials and methods: A community-based cross-sectional study was conducted from March, 2021 to October, 2021 in Debre Markos town. A simple random sampling technique was used to select 165 fully vaccinated children aged 5–12 years old. A serum sample was used to determine hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis B surface antibody titer (anti-HBs) using ELISA. Results: The seroprevalence of HBsAg and anti-HBc anti-body was found to be 4.2% and 4.8% respectively. Of 165 fully vaccinated children, 129 (78.2%) had anti-HBs titer ≥ 10 mIU/ml. Among 129 sero-protected children, 76 (58.9%) were hypo-responders whereas the rest 53 (41.1%) were good responders. Those children within the age group of 5–7 years were 2.9 times (AOR: 2.873, 95% CI: 1.156, 7.141) (P<0.023) more likely to respond to HBV vaccine. Multivariate logistic regression revealed that children who were born from HBV positive mothers (AOR 3.917, 95% CI: 1.456, 5.365, P<0.027) and those who had history of injectable medications (AOR 9.232, 95% CI: 1.503, 11.697, P<0.016) were more likely to be HBsAg positive. Children who had history of hospital admission (AOR 6.973, 95% CI: 1.495, 8.530, P<0.013) were more likely to be anti-HBcAb positive. Conclusions: There was an intermediate prevalence of childhood HBV infection despite being vaccinated suggesting low protective efficacy of hepatitis B vaccine in the study area. [ABSTRACT FROM AUTHOR]

Background: Tuberculous lymphadenitis (TBLN) diagnosis has been a true challenge solely by clinical evidence in developing countries, due to limited the diagnostic facility on hand. However, the availability and affordability of available diagnostic tools in resource-limited settings like Ethiopia necessitates the quest for other techniques with added value over direct Z-N microscopy. Therefore, we aimed at to assess whether the concentration of lymph node aspirate similarly improves the detection rate of tuberculous lymphadenitis or not.Materials and Methods: A cross-sectional study design was conducted on 132 individual subjects presumptive for tuberculous lymphadenitis from February to October 2013 in Addis Ababa, Ethiopia. Fine needle aspirate (FNA) samples were collected from the cases and cultured on Löwenstein-Jensen (LJ) slants. Identification of species and strains of mycobacteria was made by region of difference (RD) based polymerase chain reaction (PCR). Data entry and statistical analyses were performed by SPSS version 20. The confidence level of 95% was used for statistical significance.Result: A total of 132 study subjects were included in our study. Of these 56.1% (74/132) were positive for M. tuberculosis on culture. The detection rate of direct smear microscopy and the concentration method were 29.5 and 65.2% respectively. The sensitivity of direct smear microscopy was 43.2%, for concentrated smear microscopy 94.5%, for PCR 93.2% and for cytomorphology 95.4%. The level of agreement of concentrated ZN smear microscopy was 0.62 which was very similar with kappa of 0.58 of molecular (PCR) technique. AFB positivity by the concentration method and molecular method was increased in caseous aspirates as compared to purulent and hemorrhagic aspirates though it was not statistically significant (p-value = 0.18) and (p = 0.62) respectively.Conclusion: The concentration of FNA (Fine Needle Aspirate) aspirates for acid-fast smear microscopy similarly improves the sensitivity of acid fast bacilli in diagnosing of TBLN. [ABSTRACT FROM AUTHOR]

Dengue fever is a mosquito-borne viral infection, with rising incidence globally. Eastern Ethiopia has had dengue fever outbreaks in recent years. However, the extent to which the infection contributes to hospital presentation among children with fever in southern Ethiopia is unknown. We examined 407 stored plasma samples collected to investigate the aetiology of fever in children aged at least 2 months and under 13 years presenting to the outpatient of the largest tertiary hospital in southern Ethiopia. We analyzed samples for dengue virus non-structural 1 antigen using enzyme-linked immunosorbent assay. The median (interquartile range) age of the 407 children examined was 20 (10–48) months, and 166 (40.8%) of the children were females. Of 407 samples analyzed, 9 (2.2%) were positive for dengue virus non-structural 1 antigen, of whom 2 were initially treated with antimalarial drugs despite having negative malaria microscopy, and 1 of the 8 patients had a persistent fever at the seventh day of follow-up time. The presence of active dengue virus infection in the study area highlights the need for studies at the community level as well as the integration of dengue diagnostics into fever-management strategies. Further research to characterize circulating strains is warranted. [ABSTRACT FROM AUTHOR]

Livestock value chains constitute a source of livelihood for meat and milk value chain actors in Ethiopia, from dairy farmers to other associated value chain actors such as milk traders, abattoir workers, public health officials, veterinarians, butcheries selling meats, milk cooperatives, artisanal milk processors, and transporters. The development of these livestock value chains, however, is constrained by poor food safety and quality, while consumers are also exposed to public health risks due to milk and meat value chain actors’ food handling and hygiene practices. This study used Photovoice and participant observation to explore meat and milk value chain actors’ food handling and hygiene practices in suburban areas of Addis Ababa and neighbouring Oromia in Ethiopia. The results of this study reveal that milk and meat value chain actors’ food handling practices are not aligned with the recommended Ethiopian food safety and quality standards. Low compliance with food safety and quality standards reflected a combination of factors such as lack of incentives, poor road infrastructure and low enforcement of food safety standards. Participatory and visual research methods enable a researcher to collect context-aware data that can lead to the development of policies and intervention strategies that reflect local needs and priorities. The results of this study affirm the need to identify socially acceptable and economically viable policies and intervention strategies that are acceptable to all chain actors; and suggest there is an imperative to train milk and meat value chain actors on good hygiene handling practices, improve road infrastructure, and facilitate access equipment such as fridges and freezers that can contribute to maintaining food safety and quality. [ABSTRACT FROM AUTHOR]

With the widespread use of Integrase strand transfer inhibitors (INSTIs), surveillance of HIV-1 pretreatment drug resistance is critical in optimizing antiretroviral treatment efficacy. However, despite the introduction of these drugs, data concerning their resistance mutations (RMs) is still limited in Ethiopia. Thus, this study aimed to assess INSTI RMs and polymorphisms at the gene locus coding for Integrase (IN) among viral isolates from ART-naive HIV-1 infected Ethiopian population. This was a cross-sectional study involving isolation of HIV-1 from plasma of 49 newly diagnosed drug-naive HIV-1 infected individuals in Addis-Ababa during the period between June to December 2018. The IN region covering the first 263 codons of blood samples was amplified and sequenced using an in-house assay. INSTIs RMs were examined using calibrated population resistance tool version 8.0 from Stanford HIV drug resistance database while both REGA version 3 online HIV-1 subtyping tool and the jumping profile Hidden Markov Model from GOBICS were used to examine HIV-1 genetic diversity. Among the 49 study participants, 1 (1/49; 2%) harbored a major INSTIs RM (R263K). In addition, blood specimens from 14 (14/49; 28.5%) patients had accessory mutations. Among these, the M50I accessory mutation was observed in a highest frequency (13/49; 28.3%) followed by L74I (1/49; 2%), S119R (1/49; 2%), and S230N (1/49; 2%). Concerning HIV-1 subtype distribution, all the entire study subjects were detected to harbor HIV-1C strain as per the IN gene analysis. This study showed that the level of primary HIV-1 drug resistance to INSTIs is still low in Ethiopia reflecting the cumulative natural occurrence of these mutations in the absence of selective drug pressure and supports the use of INSTIs in the country. However, continues monitoring of drug resistance should be enhanced since the virus potentially develop resistance to this drug classes as time goes by. [ABSTRACT FROM AUTHOR]

Background. Drug-resistant tuberculosis (TB) epidemic in high-TB-incidence countries, particularly Ethiopia, remains a significant challenge. As a result, we investigated the drug resistance, common gene mutation, and molecular characterization of mycobacterial isolates from patients with suspected tuberculous lymphadenitis (TBLN). Methodology. A cross-sectional study of 218 FNA samples from TBLN patients inoculated on Lowenstein-Jensen media was carried out. The culture isolates were identified as MTB by polymerase chain reaction (PCR) and the difference-9 (RD9) test region. In addition, the GenoType MTBDRplus assay tested the first and second-line MTB drugs, and the spoligotyping strain-dependent polymorphism test was determined. Results. Among the 50 culture-positive isolates, 14% (7/50) had drug resistance caused by a gene mutation. Out of these, 4 (8%) isolates were mono-resistant to isoniazid drug, which is caused by a gene mutation in katG in the region of interrogated at codon 315 in the amino acid sequence of S315T1, and 3 (6%) isolates were resistant to both rifampicin and isoniazid drugs. The mutation was observed for katG (at codon 315 with a change in the sequence of amino acid S315T) and rpoB (at codon 530–533 with a change in the sequence of amino acid S531L (S450L)) genes. The most prevalent spoligotypes were orphan and SIT53 strains. Conclusion. The predominance of INH mono-resistance poses a critical risk for the potential development of MDR-TB, as INH mono-resistance is a typical pathway to the occurrence of MDR-TB. The orphan and SIT53 (T) strains were the most common in the study area, and a drug-resistant strain caused by a common gene mutation could indicate the transmission of clonal-resistant strains in the community. [ABSTRACT FROM AUTHOR]

Background: Leprosy or Hansen's disease is known to cause disability and disfigurement. A delay in case detection among leprosy patients can lead to severe outcomes. In Ethiopia, the disability rates caused by leprosy among new cases are relatively high compared to other endemic countries. This suggests the existence of hidden leprosy cases in the community and a delay in timely detection. To reduce disability rates, it is crucial to identify the factors associated with this delay. This study aimed to determine the extent of delay in case detection among leprosy cases in Eastern Ethiopia. Methods: This health-institution based cross-sectional explorative study was conducted in January and February 2019 among 100 leprosy patients diagnosed ≤6 months prior to inclusion. A structured questionnaire was used to collect data, including the initial onset of symptoms, and the reasons for delayed diagnosis. Descriptive statistics, including percentages and medians, were used to describe the case detection delay. Logistic regression analysis was carried out to evaluate the predictors of delay in case detection of >12 months. Findings: The median age of patients was 35 years, with a range of 7 to 72 years. The majority were male (80%) and rural residents (90%). The median delay in case detection was 12 months (interquartile range 10–36 months) among the included patients. The mean delay in case detection was 22 months, with a maximum delay of 96 months. The overall prevalence of disability among the study population was 42% (12% grade I and 30% grade II). Fear of stigma (p = 0.018) and experiencing painless symptoms (p = 0.018) were highly associated with a delay in case detection of >12 months. Conclusions: Being afraid of stigma and having painless symptoms, which are often misinterpreted as non-alarming at the onset of the disease, were associated with a delay in case detection. This study showed the need to increase knowledge on early symptoms of leprosy among affected communities. Furthermore, it is important to support initiatives that reduce leprosy related stigma and promote health worker training in leprosy control activities. Author summary: Leprosy, also called Hansen's disease, is a chronic infectious disease that may result in devastating disabilities. The disability rate among new leprosy patients in Ethiopia is high compared to other countries. A delay in case detection is a major factor contributing to the development of disability. Late diagnosis also fosters ongoing transmission, increasing the incidence of the disease. We aimed to determine the extent of the detection delay and find the reasons for this delay in eastern Ethiopian districts, endemic for leprosy. One hundred leprosy patients who recently started multi-drug therapy were included in the study. The median detection delay was one year among all patients. About half of the patients had sought treatment from health institutions within one year after the onset of their first symptoms. Longer delays among leprosy patients were associated with a fear of stigma and painless symptoms at an early stage of the disease. This indicates that it is vital to improve community knowledge of leprosy symptoms and to take initiatives that reduce stigma. This should improve health-seeking behaviour and may prevent the development of disability as well as halt transmission. [ABSTRACT FROM AUTHOR]

Lipoarabinomannan ( LAM) is a virulent factor used for entry and survival of Mycobacterium tuberculosis ( Mtb) in macrophages. Although the role of LAM for the diagnosis of tuberculosis ( TB) has been extensively investigated, its cytokine response during natural Mtb infection in humans is largely unknown. In this study, LAM-specific IFN-γ, TNF-α, and IL-10 levels following whole blood assay were measured in untreated pulmonary TB patients, their contacts and community controls at baseline. In treated patients and contacts, cytokines were also measured at 6 and 12 months. At entry, 52.8% and 74.8% of controls and contacts were QFT- GIT positive, respectively. At baseline, untreated TB patients and contacts had significantly lower IFN-γ and TNF-α response compared to community controls (p < 0.0001). Besides, untreated patients had significantly higher TNF-α and IL-10 response compared to their contacts (p < 0.0001). At 6 months, contacts and treated TB patients had significantly increased INF-γ and TNF-α response (p < 0.0001). In TB patients, IFN-γ increased 10-fold following chemotherapy suggesting its potential role for treatment monitoring. The data suggests that LAM might have an anti-inflammatory effect during clinical TB and early Mtb infection. The data also suggests that LAM-induced IFN-γ and TNF-α could be used as biomarkers of protective immunity. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is among the leading causes of morbidity and mortality. The causative agent, Mycobacterium tuberculosis (Mtb), has evolved virulent factors for entry, survival, multiplication and immune evasion. Rv2031 (also called alpha crystallin, hspX, 16-kDa antigen), one of the most immunogenic latency antigens, is believed to play a key role in long-term viability of Mtb. Here, we report the dynamics of pro-inflammatory (IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokines against Rv2031 using whole blood assay in human cohorts in a TB endemic setting. Cytokine responses to ESAT-6-CFP-10 were also measured for comparison. Blood samples were collected from smear positive pulmonary TB patients and their contacts at baseline, 6 and 12 months, and from community controls at entry. At baseline, 54.4% of controls and 73.2% of contacts were QFT-GIT test positive. Baseline IFN-γ, TNF-α and IL-10 responses to Rv2031 were significantly higher in controls compared to contacts and untreated patients (p<0.001). Furthermore, untreated patients had significantly higher TNF-α and IL-10 responses to Rv2031 compared to contacts (p<0.001). In contacts and treated patients, IFN-γ, TNF-α and IL-10 responses to Rv2031 significantly increased over 12 months (p<0.0001) and became comparable with the corresponding levels in controls. There was a positive and significant correlation between Rv2031 and ESAT-6-CFP-10 specific cytokine responses in each study group. The fact that the levels of IFN-γ, TNF-α and IL-10 against Rv2031 were highest during latent TB infection may indicate their potential as markers of protection against TB. Taken together, the findings of this study suggest the potential of IFN-γ, TNF-α and IL-10 against Rv2031 as biomarkers of the host response to Mtb during convalescence from, and the absence of, active tuberculosis. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are crucial effector cells of the innate immune response to viral infections, including HIV, through cytolytic activity and the production of cytokines with anti-HIV activities. We recruited 15 treatment naïve HIV patients and 16 healthy controls (HC) to assess NK cell subsets or expression of multiple markers by flow cytometry. The frequency of circulating CD56brightCD16−ve and CD56dimCD16bright NK cell subsets was significantly lower among the HIV group than in HC. The CD56−veCD16bright subset was higher in HIV patients, but this was only apparent when gated among total NK cells, not total lymphocytes. NK cells among HIV participants also showed a lower and higher frequency of CD8 and HLA-DR expressing cells, respectively. In addition, CD7 median fluorescent intensity and CD2+CD7− frequencies were significantly lower in HIV patients. A distinct population of KIR3DL1/S1 cells was unexpectedly higher among CD56brightCD16−ve NK cells in HIV patients. In conclusion, this study in the Ethiopian setting confirms many previous findings, but the down-regulation of CD7 and enhanced KIR3DL1/S1 within the CD56bright subsets have not been widely reported among HIV patients and merit further research. [ABSTRACT FROM AUTHOR]

Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg in the presence of HBV DNA in the serum and/or liver tissue remains a potential risk of transmission and diseases progression among different population groups. It could be associated with asymptomatic case up to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The objective of this study was to assess the magnitude and characteristics of OBI among patients with CLD of unidentified cause in Addis Ababa, Ethiopia. The study was conducted at the gastroenterology & hepatology referral clinic of three government and two private hospitals in Addis Ababa. Known CLD patients as evidenced by clinical and imaging criteria and/or with HBV surface antigen (HBsAg) negative results using rapid test kit were included. ELISA serological test to anti-HBc Ab, anti HBsAg Ab, and HBsAg were determined using BIORAD kits [https://www.bio-rad.com]. HBV-DNA was amplified, and viral loads were determined by quantitative real-time PCR using Abbott m2000rt platform following the manufacturer's instructions. Data analysis was done using SPSS version 20.A total of 48 CLD patients with no identified cause for their liver disease were identified during the study period. All the patients had evidence of CLD by clinical and imaging criteria and nine were excluded. Three (7.69%) of the 39 patients tested positive for HBsAg test done by ELISA making the negative predictive value of the rapid test kits 92.3% compared to ELISA. The remaining 36 patients had serology test for HBV and 16 (44.4%) had positive anti-HBV core antibody. Two (5.56%) of the 36 patients with HBV viral load determination had detectable HBV DNA suggesting presence of an occult hepatitis B infection. Occult hepatitis B infection is found to be an aetiology among CLD patients labelled as having no identified cause by the current standard of care using rapid HBsAg kits in a subset of patients in Ethiopia. This study signifies the high rate of OBI and past evidence of HBV infection among CLD patients and thus nucleic acid testing and/or anti-HBc shall be integrated to the routine health care system to minimize HBV infection risk of transmission and to enhance patient care. [ABSTRACT FROM AUTHOR]

Background: Sepsis due to multidrug resistant (MDR) bacteria is a growing public health problem mainly in low-income countries. Methods: A multicenter study was conducted between October 2019 and September 2020 at four hospitals located in central (Tikur Anbessa and Yekatit 12), southern (Hawassa) and northern (Dessie) parts of Ethiopia. A total of 1416 patients clinically investigated for sepsis were enrolled. The number of patients from Tikur Anbessa, Yekatit 12, Dessie and Hawassa hospital was 501, 298, 301 and 316, respectively. At each study site, blood culture was performed from all patients and positive cultures were characterized by their colony characteristics, gram stain and conventional biochemical tests. Each bacterial species was confirmed using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI TOF). Antimicrobial resistance pattern of bacteria was determined by disc diffusion. Logistic regression analysis was used to assess associations of dependent and independent variables. A p-value < 0.05 was considered as statistically significant. The data was analyzed using SPSS version 25. Results: Among 1416 blood cultures performed, 40.6% yielded growth. Among these, 27.2%, 0.3% and 13.1%, were positive for pathogenic bacteria, yeast cells and possible contaminants respectively. Klebsiella pneumoniae (26.1%), Klebsiella variicola (18.1%) and E. coli (12.4%) were the most frequent. Most K. variicola were detected at Dessie (61%) and Hawassa (36.4%). Almost all Pantoea dispersa (95.2%) were isolated at Dessie. Rare isolates (0.5% or 0.2% each) included Leclercia adecarboxylata, Raoultella ornithinolytica, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Burkholderia cepacia, Kosakonia cowanii and Lelliottia amnigena. Enterobacteriaceae most often showed resistance to ampicillin (96.2%), ceftriaxone (78.3%), cefotaxime (78%), cefuroxime (78%) and ceftazidime (76.4%). MDR frequency of Enterobacteriaceae at Hawassa, Tikur Anbessa, Yekatit 12 and Dessie hospital was 95.1%, 93.2%, 87.3% and 67.7%, respectively. Carbapenem resistance was detected in 17.1% of K. pneumoniae (n = 111), 27.7% of E. cloacae (n = 22) and 58.8% of Acinetobacter baumannii (n = 34). Conclusion: Diverse and emerging gram-negative bacterial etiologies of sepsis were identified. High multidrug resistance frequency was detected. Both on sepsis etiology types and MDR frequencies, substantial variation between hospitals was determined. Strategies to control MDR should be adapted to specific hospitals. Standard bacteriological services capable of monitoring emerging drug-resistant sepsis etiologies are essential for effective antimicrobial stewardship. [ABSTRACT FROM AUTHOR]