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Population history-focused DNA and ancient DNA (aDNA) research in Africa has dramatically increased in the past decade, enabling increasingly fine-scale investigations into the continent's past. However, while international interest in human genomics research in Africa grows, major structural barriers limit the ability of African scholars to lead and engage in such research and impede local communities from partnering with researchers and benefitting from research outcomes. Because conversations about research on African people and their past are often held outside Africa and exclude African voices, an important step for African DNA and aDNA research is moving these conversations to the continent. In May 2023 we held the DNAirobi workshop in Nairobi, Kenya and here we synthesize what emerged most prominently in our discussions. We propose an ideal vision for population history-focused DNA and aDNA research in Africa in ten years' time and acknowledge that to realize this future, we need to chart a path connecting a series of "landmarks" that represent points of consensus in our discussions. These include effective communication across multiple audiences, reframed relationships and capacity building, and action toward structural changes that support science and beyond. We concluded there is no single path to creating an equitable and self-sustaining research ecosystem, but rather many possible routes linking these landmarks. Here we share our diverse perspectives as geneticists, anthropologists, archaeologists, museum curators, and educators to articulate challenges and opportunities for African DNA and aDNA research and share an initial map toward a more inclusive and equitable future.
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ADN Antiguo , Genética de Población , Humanos , ADN Antiguo/análisis , África , Genómica , Población Negra/genéticaRESUMEN
In our previous cross-sectional study, multiple species of Campylobacter were detected (88%) in stool samples from children (12 to 14 months of age) in rural eastern Ethiopia. This study assessed the temporal fecal carriage of Campylobacter in infants and identified putative reservoirs associated with these infections in infants from the same region. The prevalence and load of Campylobacter were determined using genus-specific real-time PCR. Stool samples from 106 infants (n = 1,073) were collected monthly from birth until 376 days of age (DOA). Human stool samples (mothers and siblings), livestock feces (cattle, chickens, goats, and sheep), and environmental samples (soil and drinking water) from the 106 households were collected twice per household (n = 1,644). Campylobacter was most prevalent in livestock feces (goats, 99%; sheep, 98%; cattle, 99%; chickens, 93%), followed by human stool samples (siblings, 91%; mothers, 83%; infants, 64%) and environmental samples (soil, 58%; drinking water, 43%). The prevalence of Campylobacter in infant stool samples significantly increased with age, from 30% at 27 DOA to 89% at 360 DOA (1% increase/day in the odds of being colonized) (P < 0.001). The Campylobacter load increased linearly (P < 0.001) with age from 2.95 logs at 25 DOA to 4.13 logs at 360 DOA. Within a household, the Campylobacter load in infant stool samples was positively correlated with the load in mother stool samples (r2 = 0.18) and soil collected inside the house (r2 = 0.36), which were in turn both correlated with Campylobacter loads in chicken and cattle feces (0.60 < r2 < 0.63) (P < 0.01). In conclusion, a high proportion of infants are infected with Campylobacter in eastern Ethiopia, and contact with the mother and contaminated soil may be associated with early infections. IMPORTANCE A high Campylobacter prevalence during early childhood has been associated with environmental enteric dysfunction (EED) and stunting, especially in low-resource settings. Our previous study demonstrated that Campylobacter was frequently found (88%) in children from eastern Ethiopia; however, little is known about potential Campylobacter reservoirs and transmission pathways leading to infection of infants by Campylobacter during early growth. In the longitudinal study presented here, Campylobacter was frequently detected in infants within the 106 surveyed households from eastern Ethiopia, and the prevalence was age dependent. Furthermore, preliminary analyses highlighted the potential role of the mother, soil, and livestock in the transmission of Campylobacter to the infant. Further work will explore the species and genetic composition of Campylobacter in infants and putative reservoirs using PCR and whole-genome and metagenomic sequencing. The findings from these studies can lead to the development of interventions to minimize the risk of transmission of Campylobacter to infants and, potentially, EED and stunting.
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Infecciones por Campylobacter , Campylobacter , Heces , Humanos , Animales , Campylobacter/genética , Campylobacter/aislamiento & purificación , Heces/microbiología , Ganado/microbiología , Etiopía , Recién Nacido , Lactante , Prevalencia , Infecciones por Campylobacter/epidemiología , Infecciones por Campylobacter/microbiología , Estudios Longitudinales , Población Rural , Microbiología Ambiental , Carga BacterianaRESUMEN
INTRODUCTION: Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care. OBJECTIVE: We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up. METHODS: A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed. RESULTS: The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma. CONCLUSION: The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.
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Tamizaje Masivo , Tuberculosis , Humanos , Tuberculosis/diagnóstico , Tamizaje Masivo/métodos , Investigación Cualitativa , África Oriental , Evaluación de Programas y Proyectos de SaludRESUMEN
BACKGROUND: In most African countries where a legitimate vital registration system is lacking, physicians often review verbal autopsy (VA) data to determine the cause of death, while there are concerns about the routine practicality, accuracy, and reliability of this procedure. In Ethiopia where the burden of tuberculosis (TB) remains unacceptably high, reliable VA data are needed to guide intervention strategies. This study aimed to validate the InterVA model against the physician VA in tracking TB-related mortality in Ethiopia. METHODS: From a sample of deaths in Addis Ababa, Ethiopia, VAs were conducted on TB-related mortality, physician-certified verbal autopsy (PCVA) through multiple steps to ascertain the causes of death. InterVA model was used to interpret the causes of death. Estimates of TB-related deaths between physician reviews and the InterVA model were compared using Cohen's Kappa (k), Receiver-operator characteristic (ROC) curve analysis, sensitivity, and specificity to compare agreement between PCVA and InterVA. RESULTS: A total of 8952 completed PCVA were used. The InterVA model had an optimal likelihood cut-off point sensitivity of 0.64 (95% CI: 59.0-69.0) and specificity of 0.95 (95% CI: 94.9-95.8). The area under the ROC curve was 0.79 (95% CI: 0.78-0.81). The level of agreement between physician reviews and the InterVA model to identifying TB-related mortality was moderate (k = 0.59, 95% CI: 0.57-0.61). CONCLUSION: The InterVA model is a viable alternative to physician review for tracking TB-related causes of death in Ethiopia. From a public health perspective, InterVA helps to analyze the underlying causes of TB-related deaths cost-effectively using routine survey data and translate to policies and strategies in resource-constrained countries.
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Médicos , Tuberculosis , Autopsia/métodos , Causas de Muerte , Etiopía/epidemiología , Humanos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
BACKGROUND: Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain. OBJECTIVE: To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once. DESIGN: Randomized trial. (ClinicalTrials.gov: NCT02980016). SETTING: South Africa, Ethiopia, and Mozambique. PARTICIPANTS: Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis. INTERVENTION: Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture. MEASUREMENTS: Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months. RESULTS: Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]). LIMITATION: If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness. CONCLUSION: Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy. PRIMARY FUNDING SOURCE: The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.
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Antituberculosos/uso terapéutico , Infecciones por VIH/complicaciones , Isoniazida/uso terapéutico , Rifampin/análogos & derivados , Tuberculosis Pulmonar/prevención & control , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Etiopía , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Isoniazida/administración & dosificación , Masculino , Mozambique , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Sudáfrica , Adulto JovenRESUMEN
There has been high interest in the use of traditional medicines for COVID-19 from early in the course of the pandemic. Significant advances in the science of ethnopharmacology have helped to introduce chemical entities identified from natural sources into modern medicine. However, the wider integration of natural products into the modern drug discovery process will require enhanced collaboration amongst the pharmaceutical industry, academic research units, regulatory bodies, ethics review committees and local, regional, continental and international organizations. Revisiting this topic holds promise of benefit for both the current and future pandemics.
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COVID-19 , Etnofarmacología , Humanos , Medicina Tradicional , Pandemias , SARS-CoV-2RESUMEN
BACKGROUND: Proper specimen collection is central to improving patient care by ensuring optimal yield of diagnostic tests, guiding appropriate management, and targeting treatment. The purpose of this article is to describe the development and implementation of a training-of-trainers educational program designed to improve clinical culture specimen collection among healthcare personnel (HCP) in Ethiopia. METHODS: A Clinical Specimen Collection training package was created consisting of a Trainer's Manual, Reference Manual, Assessment Tools, Step-by-Step Instruction Guides (i.e., job aides), and Core Module PowerPoint Slides. RESULTS: A two-day course was used in training 16 master trainers and 47 facility-based trainers responsible for cascading trainings on clinical specimen collection to HCP at the pre-service, in-service, or national-levels. The Clinical Specimen Collection Package is offered online via The Ohio State University's CANVAS online platform. CONCLUSIONS: The training-of-trainers approach may be an effective model for development of enhanced specimen collection practices in low-resource countries.
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Personal de Salud , Manejo de Especímenes , Etiopía , HumanosRESUMEN
BACKGROUND: Africa's economic transformation relies on a radical transformation of its higher education institutions. The establishment of regional higher education Centres of Excellence (CoE) across Africa through a World Bank support aims to stimulate the needed transformation in education and research. However, excellence is a vague, and often indiscriminately used concept in academic circles. More importantly, the manner in which aspiring institutions can achieve academic excellence is described inadequately. The main objective of this paper is to describe the core processes of excellence as a prerequisite to establishing academic CoE in Africa. METHODS: The paper relies on our collaborative discussions and real-world insight into the pursuit of academic excellence, a narrative review using Pubmed search for a contextual understanding of CoEs in Africa supplemented by a Google search for definitions of CoEs in academic contexts. RESULTS: We identified three key, synergistic processes of excellence central to institutionalizing academic CoEs: participatory leadership, knowledge management, and inter-disciplinary collaboration. (1) Participatory leadership encourages innovations to originate from the different parts of the organization, and facilitates ownership as well as a culture of excellence. (2) Centers of Excellence are future-oriented in that they are constantly seeking to achieve best practices, informed by the most up-to-date and cutting-edge research and information available. As such, the process by which centres facilitate the flow of knowledge within and outside the organization, or knowledge management, is critical to their success. (3) Such centres also rely on expertise from different disciplines and 'engaged' scholarship. This multidisciplinarity leads to improved research productivity and enhances the production of problem-solving innovations. CONCLUSION: Participatory leadership, knowledge management, and inter-disciplinary collaborations are prerequisites to establishing academic CoEs in Africa. Future studies need to extend our findings to understand the processes key to productivity, competitiveness, institutionalization, and sustainability of academic CoEs in Africa.
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Becas , Liderazgo , África , Humanos , Encuestas y Cuestionarios , UniversidadesRESUMEN
BACKGROUND: Management of patients with breast cancer undergoing chemotherapy is complicated by a very high rate of adverse drug reactions which is even more challenging in developing countries like Ethiopia where the toxicity profile of chemotherapy is lacking. The present study aimed at evaluating the toxicity profile of Doxorubicin-Cyclophosphamide (AC) and Doxorubicin-CyclophosphamideâPaclitaxel (ACâT) regimens among 146 patients with breast cancer in Ethiopia. METHODS: This prospective cohort study, with the median of six months' follow-up, was conducted from January 1 to September 30, 2017 GC at the only nationwide oncology center, Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia. Seventy-one patients received AC, while 75 received AC-T regimen. The toxicity with the highest grade during any cycle was considered as the toxicity grade for that patient. SPSS version 22 was used for analysis. RESULTS: The overall frequent non-hematological adverse drug reactions reported for both regimens were fatigue 144 (98.7%), dysgeusia 142 (97.3%), skin hyperpigmentation 141 (96.6%), nausea 136 (93.2%), vomiting 129 (88.4%), gastritis 122 (83.6%), peripheral neuropathy 108 (74%), and myalgia/arthralgia 110 (75.3%). Neutropenia 107 (73.3%), leukopenia 102 (69.9%), and anemia 51 (34.9%) were the most frequent overall grade hematological toxicities reported. However, those received AC regimen suffered more from grade 2 and above leukopenia (35.2% vs. 17.3%, P = 0.014), anemia (16.9% vs. 2.7%, P = 0.004), and alkaline phosphatase increment (11.3% vs. 2.7%, P = 0.039) than AC-T regimen. On the contrary, those received AC-T regimen suffered more from severe arthralgia/myalgia (2.8% vs. 2%, P = 0.001), peripheral neuropathy (1.4% vs. 36%, P = 0.000), and gastritis (14.1% vs. 29.3%, P = 0.026) than AC regimen. Pretreatment blood cell counts, having stage IV breast tumor, older age, and lower body surface area were significant predictors of grade 2 to above hematological toxicities. Older age, arthralgia/myalgia, and skin hyperpigmentation occurred during the cohort were significant predictors of grade 2 to above oral mucositis, peripheral neuropathy, and fatigue, respectively. CONCLUSION: Patients who received the AC regimen suffered more from hematological abnormalities, while those on the AC-T regimen experienced more of non-hematological toxicities. Overall, we report high incidences of AC and AC-T regimens-induced toxicities in Ethiopian women with breast cancer, and they may require prior support based on pretreatment blood counts, age and body surface area, and close follow-up during chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Cohortes , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etiopía , Femenino , Humanos , Persona de Mediana Edad , Náusea/inducido químicamente , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Estudios ProspectivosRESUMEN
The objectives of this study were to characterize the population pharmacokinetics (PK) of efavirenz (EFV) and 8-hydroxy-efavirenz (8OHEFV) in plasma and peripheral blood mononuclear cells (PBMCs) and to explore covariates affecting the PK parameters. Fifty-one patients had steady-state 0-to-24-h concentrations of EFV and 8OHEFV in plasma with corresponding concentrations in PBMCs, while 261 patients had one or two sparse concentrations at 16 ± 1 h postdose at weeks 4 and/or 16. The pharmacogenetic markers CYP2B6*6, CYP3A5*3, CYP3A5*6, UGT2B7*2, ABCB1 (3435CâT, 3842AâG), OATP1B1*1B, and OATP1B1*5, the presence of a rifampin-based antituberculosis (anti-TB) regimen, baseline body weight and organ function values, and demographic factors were explored as covariates. EFV concentration data were well described by a two-compartment model with first-order absorption (Ka ) and absorption lag time (Alag) (Ka = 0.2 h-1; Alag = 0.83 h; central compartment clearance [CLc/F] for CYP2B6*1/*1 = 18 liters/h, for CYP2B6*1/*6 = 14 liters/h, and for CYP2B6*6/*6 = 8.6 liters/h) and PBMCs as a peripheral compartment. EFV transfer from plasma to PBMCs was first order (CLp/F = 32 liters/h), followed by capacity-limited return (Vmax = 4,400 ng/ml/h; Km = 710 ng/ml). Similarly, 8OHEFV displayed a first-order elimination and distribution to PBMCs, with a capacity-limited return to plasma. No covariate relationships resulted in a significant explanation of interindividual variability (IIV) on the estimated PK parameters of EFV and 8OHEFV, except for CYP2B6*6 genotypes, which were consistent with prior evidence. Both EFV and 8OHEFV accumulated to higher concentrations in PBMCs than in plasma and were well described by first-order input and Michaelis-Menten kinetics removal from PBMCs. CYP2B6*6 genotype polymorphisms were associated with decreased EFV and 8OHEFV clearance.
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Fármacos Anti-VIH/farmacocinética , Benzoxazinas/farmacocinética , Inductores del Citocromo P-450 CYP2B6/farmacología , Citocromo P-450 CYP2B6/genética , Infecciones por VIH/tratamiento farmacológico , Adulto , Alquinos , Fármacos Anti-VIH/sangre , Antituberculosos/uso terapéutico , Benzoxazinas/sangre , Ciclopropanos , Inductores del Citocromo P-450 CYP2B6/sangre , Demografía , Femenino , Genotipo , Infecciones por VIH/sangre , Humanos , Pruebas de Función Renal , Leucocitos Mononucleares , Pruebas de Función Hepática , Masculino , Polimorfismo Genético , Rifampin/uso terapéuticoRESUMEN
BACKGROUND & AIMS: The occurrence of drug-induced liver injury (DILI) is a major issue in all phases of drug development. To identify novel biomarker candidates associated with DILI, we utilised an affinity proteomics strategy, where antibody suspension bead arrays were applied to profile plasma and serum samples from human DILI cases and controls. METHODS: An initial screening was performed using 4594 randomly selected antibodies, representing 3450 human proteins. Resulting candidate proteins together with proposed DILI biomarker candidates generated a DILI array of 251 proteins for subsequent target analysis and verifications. In total, 1196 samples from 241 individuals across four independent cohorts were profiled: healthy volunteers receiving acetaminophen, patients with human immunodeficiency virus and/or tuberculosis receiving treatment, DILI cases originating from a wide spectrum of drugs, and healthy volunteers receiving heparins. RESULTS: We observed elevated levels of cadherin 5, type 2 (CDH5) and fatty acid-binding protein 1 (FABP1) in DILI cases. In the two longitudinal cohorts, CDH5 was elevated already at baseline. FABP1 was elevated after treatment initiation and seemed to respond more rapidly than alanine aminotransferase (ALT). The elevations were verified in the DILI cases treated with various drugs. In the heparin cohort, CDH5 was stable over time whereas FABP1 was elevated. CONCLUSIONS: These results suggest that CDH5 may have value as a susceptibility marker for DILI. FABP1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT but likely with limited predictive value for the development of severe DILI. Further studies are needed to determine the clinical utility of the proposed markers.
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Antígenos CD/sangre , Cadherinas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Proteínas de Unión a Ácidos Grasos/sangre , Acetaminofén/administración & dosificación , Adulto , Alanina Transaminasa/sangre , Biomarcadores/sangre , Femenino , Infecciones por VIH , Heparina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Proteómica , Factores de Riesgo , Tuberculosis , Adulto JovenRESUMEN
BACKGROUND: Identification of the types of strains of Mycobacterium tuberculosis (M. tuberculosis) complex causing tuberculosis (TB) could contribute to TB control program of specific geographic region as well as it could add knowledge onto the existing literature on TB worldwide. The objective of the present study was to identify the species and strains of M. tuberculosis complex causing pulmonary tuberculosis in central Ethiopia. METHODS: A health institution- based cross-sectional study was conducted on 338 smear positive TB cases visiting three hospitals between October 2012 and September 2013. Morning and spot sputum samples were collected before the starting of treatment regimens. Thus, a total of 338 pooled sputum samples collected from these cases. Samples were cultured on Löwenstein Jensen media and the isolates were identified by the region of difference (RD) 9 based polymerase chain reaction (PCR) and spoligotyping. RESULT: Of the total isolates 98.6% of the isolates were identified to be M. tuberculosis while the remaining 1.4% were identified as M. africanum. Further, typing of M. tuberculosis using spoligotyping lead to the identification of 90 different strains of M. tuberculosis. Of these strains, 32 were clustered consisting of more than one isolate while the remaining 58 strains were unique consisting of single isolate. Thus, 79.3% (223/281) of the isolates were found in the clustered while only 20.6% (58/281) of the strains were unique. Forty-five of the spolgotyping patterns were registeredin the SITVIT2 or SpolDB4 database in while the remaining 45 were notfound in the database and hence were orphan strains. The dominant strains were SIT53, SIT149, and SIT54, consisting of 43, 37 and 34 isolates, respectively. Classification of the spoligotype patterns using TB-insight RUN TB-Lineage showed that 86.8, 6.4, 5, 1.4% ofthe isolatesbelonged to the Euro-American lineage, East-African-Indian, Indo-oceanic and M. africanum, respectively. CONCLUSION: The identification of clustered and new strains using spolygotyping in present study does not give conclusive finding as spoligotyping has low discriminatory power. Thus, further identification of these isolates using mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VENTR) and or whole genome sequencing (WGS) recommended.
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Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/microbiología , Adulto , Estudios Transversales , Bases de Datos Factuales , Etiopía , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Tipificación Molecular , Mycobacterium tuberculosis/genética , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Drug-induced liver injury (DILI) is a well-recognized adverse event of anti tuberculosis drugs (ATD) possibly associated with genetic variations. The objective of this study was to perform genome-wide association study (GWAS) to identify genetic variants associated with the risk for ATD induced liver toxicity in Ethiopian patients. RESULT: Treatment-naïve newly diagnosed tuberculosis patients (n = 646) were enrolled prospectively and treated with rifampicin based short course anti-tuberculosis therapy. Whole genome genotyping was done using Illumina Omni Express Exome Bead Chip genotyping array with 951,117 single nucleotide polymorphisms (SNPs) on 48 DILI cases and 354 ATD tolerants. Replication study was carried out for 50 SNPs with the lowest P-values (top SNPs) using an independent cohort consisting of 27 DILI cases and 217 ATD tolerants. In the combined analysis, the top SNP identified was rs10946737 (P = 4.4 × 10-6, OR = 3.4, 95 % confidence interval = 2.2-5.3) in the intron of FAM65B in chromosome 6. In addition, we identified a cluster of SNPs with suggestive genome-wide significance in the intron of ATP/GTP binding protein-like 4 (AGBL4). CONCLUSION: We identified genetic variants that are potentially associated with ATD induced liver toxicity. Further studies with larger sample sizes are essential to confirm the findings.
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BACKGROUND: Cancer as a multistage process can be reversed or blocked by using chemopreventive agents. Colon cancer chemoprevention has been widely investigated using cyclooxygenase inhibitors and many other chemicals of synthetic or natural origin. This particular study was carried out to assess the colon cancer chemopreventive effect of hydro-methanol extract of Rumex abyssinicus rhizome on rats. METHOD: Colon cancer chemopreventive potential of hydro-methanol extract of Rumex abyssinicus rhizome was determined based on the number and multiplicity of aberrant crypt foci (ACF). Fifteen DMH (1, 2-dimethylhydrazine) treated and five untreated Wistar female rats were used. DMH was administered subcutaneously 30 mg/kg, after its pH was adjusted to 6.5-7. Treatment groups started receiving extract after six weeks of weekly DMH injections. The rats were divided in to four groups: Group 1 received only oral normal saline, Group 2 received DMH and normal saline, Group 3 and 4 received DMH plus 250 mg/kg and 500 mg/kg extract, respectively. Specific phytoconstituents of the plant, which were reviewed from original articles, were virtually evaluated for cyclooxygenase-2 (COX-2) inhibition. The binding energies and interactions of the phytochemicals from Rumex abyssinicus against COX-2 were determined by Autodock4.2. RESULTS: There was a statistically significant reduction (p-value < 0.05) in the number of aberrant crypt (AC) and aberrant crypt foci (ACF) at both administered doses. However, significant association (p-value > 0.05) was not observed in reducing crypt multiplicity. The docking process resulted in estimated binding energies [-6.83 kcal/mol to -7.9 kcal/mol] which are closer to the positive controls or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) [-4.55 kcal/mol to -10.84 kcal/mol]. The phytochemical-COX-2 interaction indicated the involvement of key amino acid residues in inhibition of cyclooxygenase like ARG120, TYR355, TYR385, SER530 and GLY526. CONCLUSIONS: Rumex abyssinicus had demonstrated a chemopreventive potential at post-initiation stage. As the virtual screening data suggested, COX-2 inhibition by the anthraquinones in the extract could be one mechanism for the observed chemopreventive effect.
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Antineoplásicos Fitogénicos/farmacología , Neoplasias del Colon/prevención & control , Inhibidores de la Ciclooxigenasa 2/farmacología , Rumex/química , 1,2-Dimetilhidrazina/toxicidad , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Quimioprevención , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Daño del ADN , Femenino , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas WistarRESUMEN
BACKGROUND & AIMS: There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI. METHODS: Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study. RESULTS: In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury. CONCLUSIONS: M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.
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Alanina Transaminasa/sangre , Biomarcadores/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Queratina-18/sangre , MicroARNs/sangre , Fragmentos de Péptidos/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Humanos , Sensibilidad y EspecificidadRESUMEN
Background: Pharmacogenomics research is currently revolutionizing treatment optimization by discovering molecular markers. Medicines are the cornerstone of treatment for both acute and chronic diseases. Pharmacogenomics associated treatment response varies from 20% to 95%, resulting in from lack of efficacy to serious toxicity. Pharmacogenomics has emerged as a useful tool for therapy optimization and plays a bigger role in clinical care going forward. However, in Africa, in particular in Ethiopia, such studies are scanty and not generalizing. Therefore, the objective of this review was to outline such studies, generating comprehensive evidence and identify studied variants' association with treatment responses in Ethiopian patients. Methods: The Joanna Briggs Institute's updated 2020 methodological guidelines for conducting and guidance for scoping reviews were used. We meticulously adhered to the systemic review reporting items checklist and scoping review meta-analyses extension. Results: Two hundred twenty-nine possibly relevant studies were searched. These include: 64, 54, 21, 48 and 42 from PubMed, Scopus, Google Scholar, EMBASE, and manual search, respectively. Seventy-seven duplicate studies were removed. Thirty-nine papers were rejected with justification, whereas 58 studies were qualified for full-text screening. Finally 19 studies were examined. The primary pharmacogene that was found to have a significant influence on the pharmacokinetics of efavirenz was CYP2B6. Drug-induced liver injury has frequently identified toxicity among studied medications. Conclusion and Future Perspectives: Pharmacogenomics studies in Ethiopian populations are less abundant. The studies conducted focused on infectious diseases, specifically on HAART commonly efavirenz and backbone first-line anti-tuberculosis drugs. There is a high need for further pharmacogenomics research to verify the discrepancies among the studies and for guiding precision medicine. Systematic review and meta-analysis are also recommended for pooled effects of different parameters in pharmacogenomics studies.
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One Health research has gained attention over the past few decades due to its potential to improve health challenges across the globe. However, obtaining ethics approvals for timely implementation of One Health research is a challenge in some contexts. Our study was undertaken to describe various challenges faced by researchers, research ethics committees (RECs) and members of regulatory bodies in Africa. An online survey was conducted between March and June 2021. The effect of predictors, including respondents' role (e.g., REC member, regulator and/or One Health researcher), sex, education, age, and country, on the perception of challenges and opportunities when conducting and reviewing One Health research, was investigated using multivariable linear regression models. Participants with different roles did not perceive any of the examined challenges differently during review of One Health-related research; but female participants (p = 0.026) and those with ten or more years of experience (p = 0.0325) perceived insufficient One Health knowledge as less of a challenge. Professional role was an important predictor (p = 0.025) for the perception of the establishment of a mandatory One Health review system. Respondents with multiple roles perceived the creation of ad hoc committees for review of One Health research under emergency situations to be less important (p = 0.02); and REC members perceived the creation of such committees to be less feasible (p = 0.0697). Our study showed that perceptions of the importance and feasibility of opportunities for improvement of One Health research ethics review under emergency and non-emergency situations varied across professional roles. This emphasizes the need to consider such improvement strategies; and the need for continuous and timely evaluation for improvement of ethics review of One Health and emergency research in Africa.
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Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.
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Recommended vaccination at nine months of age with the measles-containing vaccine (MCV1) has been part of Ethiopia's routine immunization program since 1980. A second dose of MCV (MCV2) was introduced in 2019 for children 15 months of age. We examined MCV1 and MCV2 coverage and the factors associated with measles vaccination status. A cross-sectional household survey was conducted among caregivers of children aged 12-35 months in selected districts of Oromia Region. Measles vaccination status was determined using home-based records, when available, or caregivers' recall. We analyzed the association between MCV1 and MCV2 vaccination status and household, caregiver, and child factors using logistic regression. The caregivers of 1172 children aged 12-35 months were interviewed and included in the analysis. MCV1 and MCV2 coverage was 71% and 48%, respectively. The dropout rate (DOR) from the first dose of Pentavalent vaccine to MCV1 was 22% and from MCV1 to MCV2 was 46%. Caregivers were more likely to vaccinate their children with MCV if they gave birth at a health facility, believe that their child had received all recommended vaccines, and know the required number of vaccination visits and doses. MCV2 coverage was low, with a high measles dropout rate (DOR). Caregivers with high awareness of MCV and its schedule were more likely to vaccinate their children. Intensified demand generation, defaulter tracking, and vaccine-stock management should be strengthened to improve MCV uptake.