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1.
Ann Hum Genet ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517013

RESUMO

Equity in access to genomic technologies, resources, and products remains a great challenge. This was evident especially during the coronavirus disease 2019 (COVID-19) pandemic when the majority of lower middle-income countries were unable to achieve at least 10% population vaccination coverage during initial COVID-19 vaccine rollouts, despite the rapid development of those vaccines. Sickle cell disease (SCD) is an inherited monogenic red blood cell disorder that affects hemoglobin, the protein that carries oxygen through the body. Globally, the African continent carries the highest burden of SCD with at least 240,000 children born each year with the disease. SCD has evolved from a treatable to a curable disease. Recently, the UK medical regulator approved its cure through clustered regularly interspaced short palindromic repeat (CRISPR)-based treatment, whereas the US Food and Drug Administration has equally approved two SCD gene therapies. This presents a remarkable opportunity to demonstrate equity in public health genomics. This CRISPR-based treatment is expensive and therefore, a need for an ambitious action to ensure that they are affordable and accessible where they are needed most and stand to save millions of lives.

2.
BMC Infect Dis ; 23(1): 587, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679664

RESUMO

Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum ß-lactamase (ESBL)-producing E. coli from African clinical settings. This hospital-based longitudinal study unraveled the genetic resistance elements in ESBL E. coli isolates from Uganda and Tanzania using whole-genome sequencing (WGS). A total of 142 ESBL multi-drug resistant E. coli bacterial isolates from both Tanzania and Uganda were sequenced and out of these, 36/57 (63.1%) and 67/85 (78.8%) originated from Uganda and Tanzania respectively. Mutations in RarD, yaaA and ybgl conferring resistances to chloramphenicol, peroxidase and quinolones were observed from Ugandan and Tanzanian isolates. We reported very high frequencies for blaCTX-M-15 with 11/18(61.1%), and blaCTX-M-27 with 12/23 (52.1%), blaTEM-1B with 13/23 (56.5%) of isolates originating from Uganda and Tanzania respectively all conferring resistance to Beta-lactam-penicillin inhibitors. We observed chloramphenicol resistance-conferring gene mdfA in 21/23 (91.3%) of Tanzanian isolates. Extraintestinal E. coli sequence type (ST) 131 accounted for 5/59 (8.4%) of Tanzanian isolates while enterotoxigenic E. coli ST656 was reported in 9/34 (26.4%) of Ugandan isolates. Virulence factors originating from Shigella dysenteriae Sd197 (gspC, gspD, gspE, gspF, gspG, gspF, gspH, gspI), Yersinia pestis CO92 (irp1, ybtU, ybtX, iucA), Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (csgF and csgG), and Pseudomonas aeruginosa PAO1 (flhA, fliG, fliM) were identified in these isolates. Overall, this study highlights a concerning prevalence and diversity of AMR-conferring elements shaping the genomic structure of multi-drug resistant E. coli in clinical settings in East Africa. It underscores the urgent need to strengthen infection-prevention controls and advocate for the routine use of WGS in national AMR surveillance and monitoring programs.Availability of WGS analysis pipeline: the rMAP source codes, installation, and implementation manual can free be accessed via https://github.com/GunzIvan28/rMAP .


Assuntos
Escherichia coli Enterotoxigênica , Humanos , Estudos Longitudinais , Virulência , Uganda/epidemiologia , Cloranfenicol , beta-Lactamases/genética
3.
Immunogenetics ; 75(3): 207-214, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37084013

RESUMO

In modern medicine, vaccination is one of the most effective public health strategies to prevent infectious diseases. Indisputably, vaccines have saved millions of lives by reducing the burden of many serious infections such as polio, tuberculosis, measles, pneumonia, and tetanus. Despite the recent recommendation by the World Health Organization (WHO) to roll out RTS,S/AS01, this malaria vaccine still faces major challenges of variability in its efficacy partly due to high genetic variation in humans and malaria parasites. Immune responses to malaria vary between individuals and populations. Human genetic variation in immune system genes is the probable cause for this heterogeneity. In this review, we will focus on human genetic factors that determine variable responses to vaccination and how variation in immune system genes affect the immunogenicity and efficacy of the RTS,S/AS01 vaccine.


Assuntos
Vacinas Antimaláricas , Malária Falciparum , Malária , Humanos , Lactente , África , Variação Genética
4.
Front Oral Health ; 3: 1004930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211252

RESUMO

Background: Dental caries is a multifactorial disease that affects many people. Even though microorganisms play a crucial role in causing dental caries, diagnosis is routinely macroscopic. In order to improve early detection especially in HIV patients who are disproportionately affected, there is need to reconcile the macroscopic and microscopic characteristics of dental caries. Therefore, the aim of this study was to characterize the oral microbiota profile along the decayed, missing, filled teeth (DMFT) index using amplicon sequencing data. Methods: Amplicon sequencing of the V6-V8 region of the 16S rRNA gene was done on DNA recovered from whole unstimulated saliva of 59 HIV positive and 29 HIV negative individuals. The microbial structure, composition and co-occurrence networks were characterized using QIIME-2, Phyloseq, Microbiome-1.9.2 and Metacoder in R. Results: We characterized the oral microbiota into 2,093 operational taxonomic units (OTUs), 21 phyla and 239 genera from 2.6 million high quality sequence reads. While oral microbiota did not cluster participants into distinct groups that track with the DMFT index, we observed the following: (a) The proportion of accessory microbiota was highest in the high DMFT category while the core size (∼50% of richness) remained relatively stable across all categories. (b) The abundance of core genera such as Stomatobaculum, Peptostreptococcus and Campylobacter was high at onset of dental caries, (c) A general difference in oral microbial biomass. (d) The onset of dental caries (low DMFT) was associated with significantly lower oral microbial entropy. Conclusions: Although oral microbial shifts along the DMFT index were not distinct, we demonstrated the potential utility of microbiota dynamics to characterize oral disease. Therefore, we propose a microbial framework using the DMFT index to better understand dental caries among HIV positive people in resource limited settings.

5.
Glob Health Action ; 15(1): 2062175, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35730550

RESUMO

Science education and research have the potential to drive profound change in low- and middle-income countries (LMICs) through encouraging innovation, attracting industry, and creating job opportunities. However, in LMICs, research capacity is often limited, and acquisition of funding and access to state-of-the-art technologies is challenging. The Alliance for Global Health and Science (the Alliance) was founded as a partnership between the University of California, Berkeley (USA) and Makerere University (Uganda), with the goal of strengthening Makerere University's capacity for bioscience research. The flagship program of the Alliance partnership is the MU/UCB Biosciences Training Program, an in-country, hands-on workshop model that trains a large number of students from Makerere University in infectious disease and molecular biology research. This approach nucleates training of larger and more diverse groups of students, development of mentoring and bi-directional research partnerships, and support of the local economy. Here, we describe the project, its conception, implementation, challenges, and outcomes of bioscience research workshops. We aim to provide a blueprint for workshop implementation, and create a valuable resource for bioscience research capacity strengthening in LMICs.


Assuntos
Países em Desenvolvimento , Saúde Global , Fortalecimento Institucional , Humanos , Pobreza , Estudantes , Universidades
6.
Antimicrob Resist Infect Control ; 11(1): 68, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35550202

RESUMO

BACKGROUND: Uganda remains one of the countries with the highest burden of TB/HIV. Drug-resistant TB remains a substantial challenge to TB control globally and requires new strategic effective control approaches. Drug resistance usually develops due to inadequate management of TB patients including improper treatment regimens and failure to complete the treatment course which may be due to an unstable supply or a lack of access to treatment, as well as patient noncompliance. METHODS: Two sputa samples were collected from Xpert MTB/RIF® assay-diagnosed multi-drug resistant tuberculosis (MDR-TB) patient at Lira regional referral hospital in northern Uganda between 2020 and 2021 for comprehensive routine mycobacterial species identification and drug susceptibility testing using culture-based methods. Detection of drug resistance-conferring genes was subsequently performed using whole-genome sequencing with Illumina MiSeq platform at the TB Supranational Reference Laboratory in Uganda. RESULTS: In both isolates, extensively drug-resistant TB (XDR-TB) was identified including resistance to Isoniazid (katG p.Ser315Thr), Rifampicin (rpoB p.Ser450Leu), Moxifloxacin (gyrA p.Asp94Gly), Bedaquiline (Rv0678 Glu49fs), Clofazimine (Rv0678 Glu49fs), Linezolid (rplC Cys154Arg), and Ethionamide (ethA c.477del). Further analysis of these two high quality genomes revealed that this 32 years-old patient was infected with the Latin American Mediterranean TB strain (LAM). CONCLUSIONS: This is the first identification of extensively drug-resistant Mycobacterium tuberculosis clinical isolates with bedaquiline, linezolid and clofazimine resistance from Uganda. These acquired resistances were because of non-adherence as seen in the patient's clinical history. Our study also strongly highlights the importance of combating DR-TB in Africa through implementing next generation sequencing that can test resistance to all drugs while providing a faster turnaround time. This can facilitate timely clinical decisions in managing MDR-TB patients with non-adherence or lost to follow-up.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Clofazimina/farmacologia , Clofazimina/uso terapêutico , Diarilquinolinas , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Humanos , Linezolida/farmacologia , Linezolida/uso terapêutico , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Uganda
7.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34591953

RESUMO

BACKGROUND: The two recent simultaneous developments of high-throughput sequencing and increased computational power have brought bioinformatics to the forefront as an important tool for effective and efficient biomedical research. Consequently, there have been multiple approaches to developing bioinformatics skills. In resource rich environments, it has been possible to develop and implement formal fully accredited graduate degree training programs in bioinformatics. In resource limited settings with a paucity of expert bioinformaticians, infrastructure and financial resources, the task has been approached by delivering short courses on bioinformatics-lasting only a few days to a couple of weeks. Alternatively, courses are offered online, usually over a period of a few months. These approaches are limited by both the lack of sustained in-person trainer-trainee interactions, which is a key part of quality mentorships and short durations which constrain the amount of learning that can be achieved. METHODS: Here, we pioneered and tested a bioinformatics training/mentorship model that effectively uses the available expertise and computational infrastructure to deliver an in-person hands-on skills training experience. This is done through a few physical lecture hours each week, guided personal coursework over the rest of the week, group discussions and continuous close mentorship and assessment of trainees over a period of 1 year. RESULTS: This model has now completed its third iteration at Makerere University and has successfully mentored trainees, who have progressed to a variety of viable career paths. CONCLUSIONS: One-year (intermediate) skills based in-person bioinformatics training and mentorships are viable, effective and particularly appropriate for resource limited settings.


Assuntos
Pesquisa Biomédica , Mentores , Pesquisa Biomédica/educação , Biologia Computacional/educação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Universidades
8.
Trop Med Infect Dis ; 6(2)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069345

RESUMO

Antimicrobial Resistance (AMR) and Healthcare Associated Infections (HAIs) are major global public health challenges in our time. This study provides a broader and updated overview of AMR trends in surgical wards of Mulago National Referral Hospital (MNRH) between 2014 and 2018. Laboratory data on the antimicrobial susceptibility profiles of bacterial isolates from 428 patient samples were available. The most common samples were as follows: tracheal aspirates (36.5%), pus swabs (28.0%), and blood (20.6%). Klebsiella (21.7%), Acinetobacter (17.5%), and Staphylococcus species (12.4%) were the most common isolates. The resistance patterns for different antimicrobials were: penicillins (40-100%), cephalosporins (30-100%), ß-lactamase inhibitor combinations (70-100%), carbapenems (10-100%), polymyxin E (0-7%), aminoglycosides (50-100%), sulphonamides (80-100%), fluoroquinolones (40-70%), macrolides (40-100%), lincosamides (10-45%), phenicols (40-70%), nitrofurans (0-25%), and glycopeptide (0-20%). This study demonstrated a sustained increase in resistance among the most commonly used antibiotics in Uganda over the five-year study period. It implies ongoing hospital-based monitoring and surveillance of AMR patterns are needed to inform antibiotic prescribing, and to contribute to national and global AMR profiles. It also suggests continued emphasis on infection prevention and control practices (IPC), including antibiotic stewardship. Ultimately, laboratory capacity for timely bacteriological culture and sensitivity testing will provide a rational choice of antibiotics for HAI.

9.
Am J Trop Med Hyg ; 105(2): 498-506, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181567

RESUMO

Reliable data on antimicrobial resistance (AMR) transmission dynamics in Uganda remains scarce; hence, we studied this area. Eighty-six index patients and "others" were recruited. Index patients were those who had been admitted to the orthopedic ward of Mulago National Referral Hospital during the study period; "others" included medical and non-medical caretakers of the index patients, and index patients' immediate admitted hospital neighbors. Others were recruited only when index patients became positive for carrying antimicrobial-resistant bacteria (ARB) during their hospital stay. A total of 149 samples, including those from the inanimate environment, were analyzed microbiologically for ARB, and ARB were analyzed for their antimicrobial susceptibility profiles and mechanisms underlying observed resistances. We describe the diagnostic accuracy of the extended-spectrum ß-lactamase (ESBL) production screening method, and AMR acquisition and transmission dynamics. Index patients were mostly carriers of ESBL-producing Enterobacteriaceae (PE) on admission, whereas non-ESBL-PE carriers on admission (61%) became carriers after 48 hours of admission (9%). The majority of ESBL-PE carriers on admission (56%) were referrals or transfers from other health-care facilities. Only 1 of 46 samples from the environment isolated an ESBL-PE. Marked resistance (> 90%) to ß-lactams and folate-pathway inhibitors were observed. The ESBL screening method's sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 50%, 90%, and 100%, respectively. AMR acquisition and transmission occurs via human-human interfaces within and outside of health-care facilities compared with human-inanimate environment interfaces. However, this remains subject to further research.


Assuntos
Infecções por Enterobacteriaceae/transmissão , Resistência beta-Lactâmica , Adolescente , Adulto , Antibacterianos/uso terapêutico , Portador Sadio/microbiologia , Criança , Pré-Escolar , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Hospitalização , Hospitais , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Admissão do Paciente , Encaminhamento e Consulta , Uganda , beta-Lactamases/metabolismo , beta-Lactamas/uso terapêutico
10.
Microb Genom ; 7(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34110280

RESUMO

The recent re-emergence of multidrug-resistant pathogens has exacerbated their threat to worldwide public health. The evolution of the genomics era has led to the generation of huge volumes of sequencing data at an unprecedented rate due to the ever-reducing costs of whole-genome sequencing (WGS). We have developed the Rapid Microbial Analysis Pipeline (rMAP), a user-friendly pipeline capable of profiling the resistomes of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) using WGS data generated from Illumina's sequencing platforms. rMAP is designed for individuals with little bioinformatics expertise, and automates the steps required for WGS analysis directly from the raw genomic sequence data, including adapter and low-quality sequence read trimming, de novo genome assembly, genome annotation, single-nucleotide polymorphism (SNP) variant calling, phylogenetic inference by maximum likelihood, antimicrobial resistance (AMR) profiling, plasmid profiling, virulence factor determination, multi-locus sequence typing (MLST), pangenome analysis and insertion sequence characterization (IS). Once the analysis is finished, rMAP generates an interactive web-like html report. rMAP installation is very simple, it can be run using very simple commands. It represents a rapid and easy way to perform comprehensive bacterial WGS analysis using a personal laptop in low-income settings where high-performance computing infrastructure is limited.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano , Genômica , Sequenciamento Completo do Genoma/métodos , Acinetobacter baumannii/genética , Animais , Antibacterianos/farmacologia , Enterobacter/genética , Enterococcus faecium/genética , Humanos , Klebsiella pneumoniae/genética , Tipagem de Sequências Multilocus , Filogenia , Plasmídeos , Staphylococcus aureus/genética
11.
Infect Drug Resist ; 14: 1733-1745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007192

RESUMO

BACKGROUND: The dual burden of road traffic accidents and antimicrobial resistance in orthopaedic infections is challenging already strained health-care systems. Limited information exists in Tanzania on antimicrobial resistance surveillance to delineate the potential sources of multi-drug-resistant bacteria for specific mitigation strategies among orthopaedic patients. METHODS: A longitudinal study was conducted at Bugando Medical Centre in Mwanza city between January and May 2020. It involved the collection of rectal swabs/stools, hand swabs, and environmental sampling to identify extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria. Participants' data were collected using a structured questionnaire and analysed to determine factors associated with ESBL colonization among index orthopaedic patients and correlates with other ESBL sources using OR (95% CI) and a cut-off p-value of ≤0.05. RESULTS: We found that 47.2% (125/265) of index patients, 77.8% (14/18) of neighbouring patients, 8.3% (2/24) of health-care workers, 72.2% (13/18) of non-medical caregivers, and 31.4% (27/86) of samples taken from the hospital environment had ESBL producers. Escherichia coli and Klebsiella spp. predominated among participants and Acinetobacter spp. predominated in the environmental samples. Patients with open fractures had increased odds of being colonized with ESBL producers [OR (95% CI): 2.08 (1.16-3.75); p=0.015]. The floor below patients' beds was commonly contaminated; however, the odds of environmental contamination decreased on the third round of sampling [OR (95% CI: 0.16 (0.04-0.67); p=0.012], apparently as a result of parallel infection prevention and control responsive measures against coronavirus disease 2019 (COVID-19). CONCLUSION: We found a high occurrence of ESBL colonization among participants and in the environmentat this tertiary hospital. The importance of routine ESBL surveillance among orthopaedic patients with open fractures on admission and strengthened decontamination of health-care premises is reiterated.

12.
Genome ; 64(5): 503-513, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33433259

RESUMO

Despite the poor genomics research capacity in Africa, efforts have been made to empower African scientists to get involved in genomics research, particularly that involving African populations. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, an initiative was set to make genomics research in Africa an African endeavor and was developed through funding from the United States' National Institutes of Health Common Fund and the Wellcome Trust. H3Africa is intended to encourage a contemporary research approach by African investigators and to stimulate the study of genomic and environmental determinants of common diseases. The goal of these endeavors is to improve the health of African populations. To build capacity for bioinformatics and genomics research, organizations such as the African Society for Bioinformatics and Computational Biology have been established. In this article, we discuss the current status of the bioinformatics infrastructure in Africa as well as the training challenges and opportunities.


Assuntos
Biologia Computacional , Genômica , África , Educação , Educação a Distância , Genoma , Genômica/educação , Humanos , Internet , Pesquisa , Uganda , Sequenciamento Completo do Genoma
13.
BMC Infect Dis ; 19(1): 853, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619192

RESUMO

BACKGROUND: Between January 2015 and July 2017, we investigated the frequency of carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Pseudomonas aeruginosa (CRPA) at the Mulago Hospital intensive care unit (ICU) in Kampala, Uganda. Carbapenemase production and carbapenemase gene carriage among CRAB and CRPA were determined; mobility potential of carbapenemase genes via horizontal gene transfer processes was also studied. METHODS: Clinical specimens from 9269 patients were processed for isolation of CRAB and CRPA. Drug susceptibility testing was performed with the disk diffusion method. Carriage of carbapenemase genes and class 1 integrons was determined by PCR. Conjugation experiments that involved blaVIM positive CRAB/CRPA (donors) and sodium azide resistant Escherichia coli J53 (recipient) were performed. RESULTS: The 9269 specimens processed yielded 1077 and 488 isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. Of these, 2.7% (29/1077) and 7.4% (36/488) were confirmed to be CRAB and CRPA respectively, but 46 were available for analysis (21 CRAB and 25 CRPA). Majority of specimens yielding CRAB and CRPA were from the ICU (78%) while 20 and 2% were from the ENT (Ear Nose & Throat) Department and the Burns Unit, respectively. Carbapenemase assays performed with the MHT assay showed that 40 and 33% of CRPA and CRAB isolates respectively, were carbapenemase producers. Also, 72 and 48% of CRPA and CRAB isolates respectively, were metallo-beta-lactamase producers. All the carbapenemase producing isolates were multidrug resistant but susceptible to colistin. blaVIM was the most prevalent carbapenemase gene, and it was detected in all CRAB and CRPA isolates while blaOXA-23 and blaOXA-24 were detected in 29 and 24% of CRAB isolates, respectively. Co-carriage of blaOXA-23 and blaOXA-24 occurred in 14% of CRAB isolates. Moreover, 63% of the study isolates carried class 1 integrons; of these 31% successfully transferred blaVIM to E. coli J53. CONCLUSIONS: CRAB and CRPA prevalence at the Mulago Hospital ICU is relatively low but carbapenemase genes especially blaVIM and blaOXA-23 are prevalent among them. This requires strengthening of infection control practices to curb selection and transmission of these strains in the hospital.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii , Infecção Hospitalar/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa , Resistência beta-Lactâmica , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Uganda , beta-Lactamases
14.
F1000Res ; 8: 150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354944

RESUMO

Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.


Assuntos
Colistina/farmacologia , Antibacterianos , Biologia Computacional , Farmacorresistência Bacteriana , Bactérias Gram-Negativas , Sequenciamento de Nucleotídeos em Larga Escala
15.
Mol Genet Genomic Med ; 7(7): e00776, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31131548

RESUMO

BACKGROUND: In Africa, health practitioners and the current knowledge of the public on genetics and genomics is still very low and yet this has potential to reduce the burden of common genetic diseases. Many initiatives have promoted genomic research, infrastructure, and capacity building in Africa. What remains to be done is to improve genomics literacy among populations and communities while utilizing an array of strategies. Genomic literacy and awareness are key in the management of genetic diseases which includes diagnosis, prevention of complications and therapy. Africa is characterized by great cultural and language diversity thereby requiring a multidisciplinary approach to improving public and community genomics literacy and engagement. However, this is further complicated by having the fact that sub-Saharan Africa is comprised of countries with the lowest literacy rates in the world. METHODS: We applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to review genomic literacy in Africa using PubMed database. RESULTS: We found very limited evidence of genomics literacy for genetic diseases in Africa. CONCLUSION: We propose a number of approaches that if adopted will significantly increase the genomic literacy and reduce the burden of genetic diseases in Africa.


Assuntos
Genômica/educação , Conhecimentos, Atitudes e Prática em Saúde/etnologia , África/epidemiologia , Atitude Frente a Saúde/etnologia , Doenças Genéticas Inatas/epidemiologia , Genômica/métodos , Genômica/tendências , Humanos , Alfabetização/tendências
16.
Can J Infect Dis Med Microbiol ; 2018: 1875217, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755620

RESUMO

HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers.

17.
BMC Infect Dis ; 18(1): 68, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29409447

RESUMO

BACKGROUND: Nosocomial infections are a major setback in the healthcare delivery system especially in developing countries due to the limited resources. The roles played by medical care equipment and work surfaces in the transmission of such organisms have inevitably contributed to the elevated mortality, morbidity and antibiotic resistances. METHODS: A total 138 samples were collected during the study from Kawolo general hospital. Swab samples were collected from various work surfaces and fomites which consisted of; beds, sink taps, infusion stands, switches, work tables and scissors. Cultures were done and the susceptibility patterns of the isolates were determined using Kirby Bauer disc diffusion method. Data was analyzed using Stata 13 and Microsoft Excel 2013 packages. RESULTS: A total of 44.2% (61/138) of the collected swab specimens represented the overall bacterial contamination of the sampled articles. Staphylococcus aureus and Klebsiella pneumoniae accounted for the highest bacterial contaminants constituting of 75.4% (46/61) and 11.5% (7/61) respectively. Infusion stands and patient beds were found to have the highest bacterial contamination levels both constituting 19.67% (12/61). The highest degree of transmission of organisms to patients was found to be statistically significant for patient beds with OR: 20.1 and P-value 8X10- 4. Vancomycin, ceftriaxone and ciprofloxacin were the most effective antibiotics with 100%, 80% and 80% sensitivity patterns among the isolates respectively. Multi-drug resistant (MDR) Staphylococcus aureus accounted for 52% (24/46) with 4% (1/24) classified as a possible extensively drug resistant (XDR) whereas Gram negative isolates had 27% (4/15) MDR strains out of which 50%(2/4) were classified as possible pan-drug resistant (PDR). CONCLUSION: The high prevalence of bacterial contaminants in the hospital work environment is an indicator of poor or ineffective decontamination. The study findings reiterate the necessity to formulate drug usage policies and re-examine effectiveness of decontamination and sterilization practices within Kawolo general hospital. We also recommend installation of a sound Microbiology unit at the hospital to take on susceptibility testing to check on the empirical use of antibiotics as a way of reducing the rampant elevations in drug resistances.


Assuntos
Klebsiella pneumoniae/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Equipamentos Cirúrgicos/microbiologia , Antibacterianos/farmacologia , Roupas de Cama, Mesa e Banho/microbiologia , Ceftriaxona/farmacologia , Ciprofloxacina/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Hospitais Gerais , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mesas Cirúrgicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Vestimenta Cirúrgica/microbiologia , Uganda , Vancomicina/farmacologia
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