Using machine learning algorithms to predict COVID-19 vaccine uptake: A year after the introduction of COVID-19 vaccines in Ghana.

The impact of vaccine hesitancy on global health is one that carries dire consequences. This was evident during the outbreak of the COVID-19 pandemic, where numerous theories and rumours emerged. To facilitate targeted actions aimed at increasing vaccine acceptance, it is essential to identify and understand the barriers that hinder vaccine uptake, particularly regarding the COVID-19 vaccine in Ghana, one year after its introduction in the country. We conducted a cross-sectional study utilizing self-administered questionnaires to determine factors, including barriers, that predict COVID-19 vaccine uptake among clients visiting a tertiary and quaternary hospital using some machine learning algorithms. Among the findings, machine learning models were developed and compared, with the best model employed to predict and guide interventions tailored to specific populations and contexts. A random forest model was utilized for prediction, revealing that the type of facility respondents visited and the presence of underlying medical conditions were significant factors in determining an individual's likelihood of receiving the COVID-19 vaccine. The results showed that machine learning algorithms can be of great use in determining COVID-19 vaccine uptake.

Development of a local antibiogram for a teaching hospital in Ghana.

Background: Antimicrobial resistance threatens adequate healthcare provision against infectious diseases. Antibiograms, combined with patient clinical history, enable clinicians and pharmacists to select the best empirical treatments prior to culture results. Objectives: To develop a local antibiogram for the Ho Teaching Hospital. Methods: This was a retrospective cross-sectional study, using data collected on bacterial isolates from January-December 2021. Samples from urine, stool, sputum, blood, and cerebrospinal fluid (CSF) were considered as well as, aspirates and swabs from wound, ears and vagina of patients. Bacteria were cultured on both enrichment and selective media including blood agar supplemented with 5% sheep blood and MacConkey agar, and identified by both the VITEK 2 system and routine biochemical tests. Data on routine culture and sensitivity tests performed on bacterial isolates from patient samples were retrieved from the hospital's health information system. Data were then entered into and analysed using WHONET. Results: In all, 891 pathogenic microorganisms were isolated from 835 patients who had positive culture tests. Gram-negative isolates accounted for about 77% of the total bacterial species. Escherichia coli (246), Pseudomonas spp. (180), Klebsiella spp. (168), Citrobacter spp. (101) and Staphylococcus spp. (78) were the five most isolated pathogens. Most of the bacterial isolates showed high resistance (>70%) to ampicillin, piperacillin, ceftazidime, ceftriaxone, cefotaxime, penicillin G, amoxicillin, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid and trimethoprim/sulfamethoxazole. Conclusions: The isolates from the various samples were not susceptible to most of the antibiotics used in the study. The study reveals the resistance patterns of E. coli and Klebsiella spp. to some antibiotics on the WHO 'Watch' and 'Reserve' lists. Using antibiograms as part of antimicrobial stewardship programmes would optimize antibiotic use and preserve their efficacy.

Sensitivity Patterns, Plasmid Profiles and Clonal Relatedness of Multi-Drug Resistant Pseudomonas aeruginosa Isolated From the Ashanti Region, Ghana.

Pseudomonas aeruginosa is a major cause of most opportunistic nosocomial infections in Ghana. The study sought to characterize P. aeruginosa isolates from market environments, poultry farms and clinical samples of patients from 2 district hospitals in the Ashanti region of Ghana. The genetic relatedness, plasmid profiles and antimicrobial sensitivity of the isolates were investigated. Culture based isolation and oprL gene amplification were used to confirm the identity of the isolates. Susceptibility testing was conducted using the Kirby Bauer disk diffusion method. Random whole genome typing of the P. aeruginosa strains was done using Enterobacterial repetitive-intergenic consensus based (ERIC) PCR assay. The most active agents against P. aeruginosa isolates were ceftazidime (90%), piperacillin (85%), meropenem, cefipeme and ticarcillin/clavulanic acid (81.6%). The isolates were most resistant to gentamycin (69%), ciprofloxacin (62.1%), ticarcillin (56.3%) and aztreonam (25%). About 65% (n = 38) of the multi-drug resistant (MDR) P. aeruginosa isolates harbored 1 to 5 plasmids with sizes ranging from 2 to 116.8 kb. A total of 27 clonal patterns were identified. Two major clones were observed with a clone showing resistance to all the test antipseudomonal agents. There is therefore a need for continued intensive surveillance to control the spread and development of resistant strains.

Antibiotic Prescribing Patterns in Ghana, Uganda, Zambia and Tanzania Hospitals: Results from the Global Point Prevalence Survey (G-PPS) on Antimicrobial Use and Stewardship Interventions Implemented.

Antimicrobial resistance (AMR) remains an important global public health issue with antimicrobial misuse and overuse being one of the main drivers. The Global Point Prevalence Survey (G-PPS) of Antimicrobial Consumption and Resistance assesses the prevalence and the quality of antimicrobial prescriptions across hospitals globally. G-PPS was carried out at 17 hospitals across Ghana, Uganda, Zambia and Tanzania. The overall prevalence of antimicrobial use was 50% (30-57%), with most antibiotics prescribed belonging to the WHO 'Access' and 'Watch' categories. No 'Reserve' category of antibiotics was prescribed across the study sites while antimicrobials belonging to the 'Not Recommended' group were prescribed infrequently. Antimicrobials were most often prescribed for prophylaxis for obstetric or gynaecological surgery, making up between 12 and 18% of total prescriptions across all countries. The most prescribed therapeutic subgroup of antimicrobials was 'Antibacterials for systemic use'. As a result of the programme, PPS data are now readily available for the first time in the hospitals, strengthening the global commitment to improved antimicrobial surveillance. Antimicrobial stewardship interventions developed included the formation of AMS committees, the provision of training and the preparation of new AMS guidelines. Other common interventions included the presentation of findings to clinicians for increased awareness, and the promotion of a multi-disciplinary approach to successful AMS programmes. Repeat PPS would be necessary to continually monitor the impact of interventions implemented. Broader participation is also encouraged to strengthen the evidence base.

Antimicrobial Prescription Pattern in Ho Teaching Hospital, Ghana: Seasonal Determination Using a Point Prevalence Survey.

A standardised Global Point Prevalence Survey (PPS) tool was used to determine the antimicrobial prescription pattern in the Ho Teaching Hospital on two separate occasions in a total of 14 wards in the hospital, including dedicated wards for paediatrics and neonates. Manually collected and anonymised data were entered, validated, analysed and reported using a web-based global PPS application. With 147 and 153 patients considered in the July 2019 and January 2020 surveys, respectively, 98 patients (66.7%) and 84 patients (54.9%) had received one or more antimicrobials. The prevalence of antimicrobial use in the adult wards was 64.3% (72/112) and 53.4% (63/118) in the first and second surveys, respectively. The prevalence in the paediatric wards was 60.0% (12/20) and 62.5% (10/16), respectively, in the two surveys, while that in the neonatal wards was 93.3% (14/15) and 57.9% (11/19), respectively. ß-lactams were the most used antibiotics in both periods. Malaria was the most common diagnosis requiring the use of antimicrobials in July 2019, accounting for 19.4% of the diagnoses, whereas in January 2020, it was skin and soft-tissue conditions (28.1%). This reflects a seasonal association between malaria and rainfall patterns. Out of the antimicrobials prescribed during each of the survey periods, 95% were used for empirical treatment, and this could be attributed to a number of reasons, including logistical challenges, among others, that require further exploration in the context of local, national and international policy recommendations.

Knowledge, Awareness and Practice with Antimicrobial Stewardship Programmes among Healthcare Providers in a Ghanaian Tertiary Hospital.

Antimicrobial resistance (AMR) is a significant problem in global health today, particularly in low- and middle-income countries (LMICs) where antimicrobial stewardship programmes are yet to be successfully implemented. We established a partnership between AMR pharmacists from a UK NHS hospital and in Ho Teaching Hospital with the aim of enhancing antimicrobial stewardship knowledge and practice among healthcare providers through an educational intervention. We employed a mixed-method approach that included an initial survey on knowledge and awareness before and after training, followed by qualitative interviews with healthcare providers conducted six months after delivery of training. This study was carried out in two phases in Ho Teaching Hospital with healthcare professionals, including pharmacists, medical doctors, nurses and medical laboratory scientists. Ethical approval was obtained prior to data collection. In the first phase, we surveyed 50 healthcare providers, including nurses (33%), pharmacists (29%) and biomedical scientists (23%). Of these, 58% of participants had engaged in continuous professional development on AMR/AMS, and above 95% demonstrated good knowledge on the general use of antibiotics. A total of 18 participants, which included four medical doctors, five pharmacists, four nurses, two midwives and three biomedical scientists, were interviewed in the second phase and demonstrated greater awareness of AMS practices, particularly the role of education for patients, as well as healthcare professionals. We found that knowledge and practice with AMS was markedly improved six months after the training session. There is limited practice of AMS in LMICs; however, through AMR-focused training, we demonstrated improved AMS skills and practice among healthcare providers in Ho Teaching Hospital. There is a need for continuous AMR training sessions for healthcare professionals in resource-limited settings.

Characterisation of rectal amoxicillin (RAMOX) for the treatment of pneumonia in children.

Access to medicines, including their availability and affordability, is a major public health challenge worldwide. This research aimed to characterise rectal formulations containing amoxicillin for the treatment of pneumonia in children under five, as an accessible alternative to existing formulations. Lipophilic Suppocire (S-NA15) and hydrophilic polyethylene glycol (PEG; 80% PEG 1500 and 20% PEG 4000, w/w) suppositories containing 250 mg amoxicillin were prepared. Hardness, apparent viscosity, uniformity of mass, uniformity of content, disintegration and dissolution time were determined. Irritation potential was screened using a slug mucosal assay and antibacterial efficacy against Staphylococcus aureus determined by isothermal microcalorimetry. Both lipophilic and hydrophilic formulations met the European Pharmacopoeia standards for suppositories when tested in vitro. They disintegrated within 30 min with rapid amoxicillin release profiles (98.6 ± 0.9%, 94.9 ± 1.2% over 30 min, respectively). Over-encapsulation of S-NA15 suppositories with hydroxypropyl methylcellulose shells slowed drug release and improved stability over 2 months. S-NA15 suppositories were classified as non-irritant and PEG suppositories only mildly irritant. Antibacterial efficacy of formulations was equivalent to amoxicillin alone. Both PEG and over-encapsulated S-NA15 rectal formulations developed in the present work have shown promise based on pre-clinical screening, and further development is justified to develop a product with commercial potential.

The potential of Streptococcus salivarius oral films in the management of dental caries: An inkjet printing approach.

The use of probiotics, which can be administered in oro-dispersible films (ODFs) and have prolonged activity in the mouth, was explored. ODFs made of xylitol and containing Streptococcus salivarius were formulated using inkjet printing and tested against Streptococcus mutans - a causative organism of dental caries. The testing of the prepared ODFs involved co-incubating an ink-jetted formulation of S. salivarius and xylitol with S. mutans and monitoring the microbial growth kinetics in real-time using isothermal microcalorimetry and colony plate counts. Cell-free supernatants (CFS) of S. salivarius were also tested against S. mutans. The phosphate solubilisation potential of S. salivarius was also determined and found to be negative, an indication that the species will not deplete phosphate from teeth. From the tests, it was observed that the formulation reduced the S. mutans population from 7.9 to 5.04 Log CFU/mL post-calorimetry (approximately 3 Log reduction) which was comparable to the 99.9% reduction expected during antimicrobial activity testing. A gradual decrease in S. mutans population was also observed with increasing of CFS of S. salivarius volumes indicative of pathogen suppression. This study demonstrates that S. salivarius can be useful in managing dental caries and ODFs of S. salivarius can be formulated easily using ink-jetting for such management.

Prevalence of vulvovaginal candidiasis among pregnant women in the Ho municipality, Ghana: species identification and antifungal susceptibility of Candida isolates.

BACKGROUND: Candida is the leading cause of vaginitis, and 75% of women have at least one episode of infection in their lives, with pregnancy being a predisposing factor. If left untreated, vulvovaginal candidiasis (VVC) can lead to chorioamnionitis with subsequent abortion, prematurity and congenital infection of the neonate. We aimed to determine the prevalence of VVC, identify the recent and most frequently occurring species of Candida in pregnant women, and determine the most effective antifungal drug of choice for treatment. METHOD: A prospective cross-sectional study in which 176 high vaginal swab samples of consented pregnant women visiting the antenatal clinic from February 2018 to April 2018 were subjected to direct gram smear and culture for Candida isolation. Candida isolates were identified using a germ tube test and HiCrome Candida differential agar. Candida isolates were then subjected to a disk diffusion method using fluconazole (25 µg), nystatin (100 units), and voriconazole (1 µg) on Mueller-Hinton agar supplemented with 2% (w/v) glucose and 0.5 µg/ml methylene blue dye to determine the susceptibility pattern as per the guidelines of the Clinical Laboratory Standard Institute (CLSI). Chi-square analysis was used to ascertain the significant association of participants' sociodemographics and clinical presentations to VVC. A univariate logistic regression model was used to identify potential risk factors of VVC. RESULTS: The prevalence of VVC among our study participants was 30.7%. Non-albicans Candida (NAC) and Candida albicans had a prevalence of 74.1 and 25.9%, respectively. Candida glabrata was the most common species, followed by Candida albicans, Candida krusei, and Candida parapsilosis. 50.0, 18.5 and 3.7% of Candida species were susceptible to voriconazole, fluconazole and nystatin, respectively, whereas 37.0, 48.1 and 9.3% of Candida species were resistant to voriconazole, fluconazole and nystatin, respectively. The majority of isolates were susceptible dose dependent to all three antifungal agents, with voriconazole being the most efficacious antifungal agent. There was no significant association between participants' socio-demographic information and clinical presentations to VVC. CONCLUSION: The prevalence of VVC was high in the study area. C. glabrata was found to be the most common cause of VVC among the pregnant women attending antenatal clinics, in the Ho Municipality region of Ghana. The majority of the Candida isolates were susceptible and resistant to voriconazole and fluconazole, respectively.

A thermal ink-jet printing approach for evaluating susceptibility of bacteria to antibiotics.

An inexpensive method for determining minimum inhibitory concentrations (MIC) using ink-jet printing to deposit drug solutions and bacterial suspensions onto agar was developed. Substrate concentrations were varied using a "Y-value", whereby a series of rectangles with the same width and colour but different heights were printed within a fixed unit area. Prior to MIC determination, the printer cartridges used were calibrated using Fast Green dye. The impact of thermal ink-jet printing on bacterial viability was assessed by colony counting and found not to be deleterious. MIC determinations were conducted by printing varying concentrations of the antibiotics onto agar-coated glass slides then printing a thin even film of a known bacterial density of Lactobacillus acidophilus. Broth microdilution was performed simultaneously to validate the results. Slides and well plates were then incubated anaerobically for 48 h. The MIC values obtained for the antibiotics used were within a permissible range for comparison.

A four-strain probiotic exerts positive immunomodulatory effects by enhancing colonic butyrate production in vitro.

Poorly formulated probiotic supplements intended for oral administration often fail to protect bacteria from the challenges of human digestion, meaning bacteria do not reach the small intestine in a viable state. As a result, the ability of probiotics to influence the human gut microbiota has not been proven. Here we show how (i) considered formulation of an aqueous probiotic suspension can facilitate delivery of viable probiotic bacteria to the gut and (ii) quantitate the effect of colonisation and proliferation of specific probiotic species on the human gut microbiota, using an in-vitro gut model. Our data revealed immediate colonisation and growth of three probiotic species in the luminal and mucosal compartments of the proximal and distal colon, and growth of a fourth species in the luminal proximal colon, leading to higher proximal and distal colonic lactate concentrations. The lactate stimulated growth of lactate-consuming bacteria, altering the bacterial diversity of the microbiota and resulting in increased short-chain fatty acid production, especially butyrate. Additionally, an immunomodulatory effect of the probiotics was seen; production of anti-inflammatory cytokines (IL-6 and IL-10) was increased and production of inflammatory chemokines (MCP-1, CXCL 10 and IL-8.) was reduced. The results indicate that the probiotic species alone do not result in a clinical effect; rather, they facilitate modulation of the gut microbiota composition and metabolic activity thereby influencing the immune response.

Use of a water-based probiotic to treat common gut pathogens.

This work reports the anti-pathogenic effect of a commercially available water-based probiotic suspension, Symprove™, against three commonly encountered infectious organisms; Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA) and Shigella sonnei. An isothermal calorimetric assay was used to the monitor growth of the species individually and in binary combinations, while colony plate counting was used to enumerate viable cell numbers. It was observed that all pathogenic species were faster growing than the probiotic bacteria in Symprove™ after inoculation into growth medium yet in all instances bacterial enumeration at the end of the experiments revealed a significant reduction in the pathogen population compared with the controls. A control population between 108 and 109 CFU/ml was obtained for E. coli and S. sonnei whilst approximately 106 CFU/ml was obtained for MRSA. Upon co-incubation for 48 h, no viable counts were obtained for E. coli; a 4-log reduction was obtained for S. sonnei whilst MRSA numbers were down to less than 10 cells/ml. The results show that Symprove™ has antipathogenic activity against E. coli, S. sonnei and MRSA.

Printing T3 and T4 oral drug combinations as a novel strategy for hypothyroidism.

Hypothyroidism is a chronic and debilitating disease that is estimated to affect 3% of the general population. Clinical experience has highlighted the synergistic value of combining triiodothyronine (T3) and thyroxine (T4) for persistent or recurrent symptoms. However, thus far a platform that enables the simultaneous and independent dosing of more than one drug for oral administration has not been developed. Thermal inkjet (TIJ) 2D printing is a potential solution to enable the dual deposition of T3 and T4 onto orodispersible films (ODFs) for therapy personalisation. In this study, a two-cartridge TIJ printer was modified such that it could print separate solutions of T3 and T4. Dose adjustments were achieved by printing solutions adjacent to each other, enabling therapeutic T3 (15-50 µg) and T4 dosages (60-180 µg) to be successfully printed. Excellent linearity was observed between the theoretical and measured dose for both T3 and T4 (R2 = 0.982 and 0.985, respectively) by changing the length of the print objective (Y-value). Rapid disintegration of the ODFs was achieved (<45 s). As such, this study for the first time demonstrates the ability to produce personalised dose combinations by TIJ printing T3 and T4 onto the same substrate for oral administration.

Personalisation of warfarin therapy using thermal ink-jet printing.

Warfarin is a widely used anticoagulant that is critical in reducing patient morbidity and mortality associated with thromboembolic disorders. However, its narrow therapeutic index and large inter-individual variability can lead to complex dosage regimes. Formulating warfarin as an orodispersible film (ODF) using thermal ink-jet (TIJ) printing could enable personalisation of therapy to simplify administration. Commercial TIJ printers are currently unsuitable for printing the milligram dosages, typically required for warfarin therapy. As such, this study aimed to modify a commercial TIJ printing system to formulate personalised warfarin ODFs containing therapeutic dosages. A TIJ printer was modified successfully with the printer functionality intact; the substrate (paper) rolling mechanism of the printer was replaced by printing onto a stationary stage. Free film substrates were composed of hydroxypropyl methylcellulose (20%w/w) and glycerol (3%w/w). The resulting ODFs were characterised for morphology, disintegration, solid-state properties and drug content. Printed film stability was assessed at 40 °C/75% relative humidity for 30 days. Therapeutic warfarin doses (1.25 and 2.5 mg) were successfully printed onto the film substrates. Excellent linearity was observed between the theoretical and measured dose by changing the warfarin feed concentration (R2 = 0.9999) and length of the print objective, i.e. the Y-value, (R2 = 0.9998). Rapid disintegration of the ODFs was achieved. As such, this study successfully formulated personalised warfarin ODFs using a modified TIJ printer, widening the range of applications for TIJ printing to formulate narrow therapeutic index drugs.

Targeted delivery of probiotics to enhance gastrointestinal stability and intestinal colonisation.

The aim of this work was to assess the viability of some commercial probiotics after exposure to gastric acid and the possibility of modifying these formulations for delivery into the distal parts of the intestines. Gastrointestinal tolerance testing was conducted for three commercial probiotics and an in-house freeze-dried Lactobacillus acidophilus strain. The contents of the commercial products and the in-house freeze-dried strain were then loaded into capsules for site-specific delivery into the colon using the Phloral® coating technology; the viability upon release was then ascertained. An assessment of the potential of these products to adhere to intestinal cells was also conducted. The results showed that all the commercial products contained the minimum number of probiotic strains as indicated on their respective packages. When gastric acid tolerance tests were performed on these products, all the commercial probiotics and the prepared freeze-dried strain demonstrated over 106 CFU reductions within 5min. When these were encapsulated for site-specific delivery into the distal parts of the gut, viabilities of approximately 90% were obtained after these capsules had been initially deposited in gastric acid for 2h. An evaluation of the ability of the probiotic formulations to adhere to intestinal cells demonstrated adhesion in the range 64-76% for the products evaluated. The need to target the delivery of probiotics into the intestines has been demonstrated here as this offers a greater potential for colonisation of the intestines once the harshness of the stomach has been overcome.

An in vitro test of the efficacy of silver-containing wound dressings against Staphylococcus aureus and Pseudomonas aeruginosa in simulated wound fluid.

An isothermal microcalorimetric assay was used to quantify the efficacy of a silver-containing wound dressing against two common wound pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. The growth patterns of the two species were unique and varied depending on the environment in which the organisms were grown. Addition of non-silver-containing dressing altered the growth kinetics while addition of silver (contained either in a dressing or as AgNO3 solution) was seen to elicit inhibition and/or kill depending on concentration. Tests were conducted in nutrient broth and simulated wound fluid. It was found that minimum inhibitory and minimum bactericidal concentration values were higher in simulated wound fluid and under anaerobic conditions. Bioavailability of silver from the wound dressing was 35% against S. aureus in nutrient broth and 68% against both species in simulated wound fluid. The data highlight the importance of developing and conducting in vitro assays in biorelevant media.