Microbial characteristics of dental caries in HIV positive individuals

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

Genomics and bioinformatics capacity in Africa: no continent is left behind

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.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies

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

Microbial contaminants isolated from items and work surfaces in the post- operative ward at Kawolo general hospital, Uganda

Abstract 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

Unraveling virulence determinants in extended-spectrum beta-lactamase-producing Escherichia coli from East Africa using whole-genome sequencing

Abstract Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum β-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 bla CTX−M−15 with 11/18(61.1%), and bla CTX−M−27 with 12/23 (52.1%), bla TEM−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

Increasing Antimicrobial Resistance in Surgical Wards at Mulago National Referral Hospital, Uganda, from 2014 to 2018—Cause for Concern?

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%), β-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

Workshop-based learning and networking: a scalable model for research capacity strengthening in low- and middle-income countries.

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