Characterization of Antibiotic Resistance in Select Tertiary Hospitals in Uganda: An Evaluation of 2020 to 2023 Routine Surveillance Data.

Antimicrobial resistance (AMR) is a public health concern in Uganda. We sought to conduct an extended profiling of AMR burden at selected Ugandan tertiary hospitals. We analyzed routine surveillance data collected between October 2020 and March 2023 from 10 tertiary hospitals. The analysis was stratified according to the hospital unit, age, gender, specimen type, and time. Up to 2754 isolates were recovered, primarily from pus: 1443 (52.4%); urine: 1035 (37.6%); and blood: 245 (8.9%). Most pathogens were Staphylococcus aureus, 1020 (37%), Escherichia coli, 808 (29.3%), and Klebsiella spp., 200 (7.3%). Only 28% of Escherichia coli and 42% of the other Enterobacterales were susceptible to ceftriaxone, while only 44% of Staphylococcus aureus were susceptible to methicillin (56% were MRSA). Enterococcus spp. susceptibility to vancomycin was 72%. The 5-24-year-old had 8% lower ampicillin susceptibility than the >65-year-old, while the 25-44-year-old had 8% lower ciprofloxacin susceptibility than the >65-year-old. The 0-4-year-old had 8% higher ciprofloxacin susceptibility. Only erythromycin susceptibility varied by sex, being higher in males. Escherichia coli ciprofloxacin susceptibility in blood (57%) was higher than in urine (39%) or pus (28%), as was ceftriaxone susceptibility in blood (44%) versus urine (34%) or pus (14%). Klebsiella spp. susceptibility to ciprofloxacin and meropenem decreased by 55% and 47%, respectively, during the evaluation period. During the same period, Escherichia coli ciprofloxacin susceptibility decreased by 40%, while Staphylococcus aureus gentamicin susceptibility decreased by 37%. Resistance was high across the Access and Watch antibiotic categories, varying with time, age, sex, specimen type, and hospital unit. Effective antimicrobial stewardship targeted at the critical AMR drivers is urgently needed.

Addressing gaps in AMR awareness in the public: an evidence-based policy brief to guide school curriculum review in Uganda.

The government of Uganda, through its Ministry of Health, previously adopted curriculum review as a mechanism to respond to public health threats such as HIV/AIDS and include content in primary and secondary schools. This approach contributes to raising public awareness, a key strategy recommended by the World Health Organization to support the global response to the threat of antimicrobial resistance (AMR). This policy brief, developed for policymakers related to school curricula, aims to advocate for and support integration of AMR content in Uganda's primary and secondary level school curricula. The policy brief supports efforts by the multisectoral National AMR Subcommittee to create awareness on this issue as part of its role in facilitating the operationalization of Uganda's National Action Plan on AMR.

Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis.

Introduction: Survival among people with HIV-associated cryptococcal meningitis (CM) remains low, particularly among women, despite the currently optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system [brain, spinal cord, and cerebrospinal fluid (CSF)] elicits the local production of cytokines, chemokines, and other biomarkers. However, no consistent diagnostic or prognostic neuroimmune signature is reported to underpin the risk of death or to identify mechanisms to improve treatment and survival. We hypothesized that distinct neuroimmune signatures in the CSF would distinguish survivors from people who died on antifungal treatment and who may benefit from tailored therapy. Methods: We considered baseline clinical features, CSF cryptococcal fungal burden, and CSF neuroimmune signatures with survival at 18 weeks among 419 consenting adults by "gender" (168 women and 251 men by biological sex defined at birth). Results: Survival at 18 weeks was significantly lower among women than among men {47% vs. 59%, respectively; hazard ratio (HR) = 1.4 [95% confidence interval (CI), 1.0 to 1.9; p = 0.023]}. Unsupervised principal component analysis (PCA) demonstrated divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, women had lower levels of programmed death ligand 1, Interleukin (IL) (IL-11RA/IL-1F30, and IL-15 (IL-15) than men (all p < 0.028). Female survivors compared with those who died expressed significant elevations in levels of CCL11 and CXCL10 chemokines (both p = 0.001), as well as increased T helper 1, regulatory, and T helper 17 cytokines (all p < 0.041). In contrast, male survivors expressed lower levels of IL-15 and IL-8 compared with men who died (p < 0.044). Conclusions: Survivors of both genders demonstrated a significant increase in the levels of immune regulatory IL-10. In conclusion, the lower survival among women with CM was accompanied by distinct differential gender-specific neuroimmune signatures. These female and male intragender-specific survival-associated neuroimmune signatures provide potential targets for interventions to advance therapy to improve the low survival among people with HIV-associated CM.

A case for routine microbial diagnostics: Results from antimicrobial susceptibility testing in post-traumatic wound infections at a Ugandan tertiary care hospital.

The global spread of antimicrobial resistance (AMR) poses an increasing challenge for clinicians in Uganda, where microbiological diagnostics are not routinely available or accessible. The aim of this study was to determine pathogen prevalence and antibiotic resistance patterns in patients with wound infections following trauma at a national referral hospital in Kampala, Uganda. In addition, the suitability of currently used empirical treatment options in this setting was evaluated. This prospective, observational study analysed antimicrobial prescriptions, culture results and antimicrobial sensitivity testing (AST) of wound swabs and blood samples from patients with clinical signs of wound infections on the trauma ward. A total of 124 patients (n = 99, 79.8% male) with a median age of 30 years (IQR 23-39) were enrolled between October 2021 and January 2022. Wound infections were classified as nosocomial in 69% of the cases. Pathogens were isolated from 122 wound swabs, yielding 238 bacterial isolates. The most prevalent pathogens were gram-negative bacteria including Escherichia coli (n = 48, 20.2%) and Acinetobacter spp. (n = 43, 18.1%). Empiric treatment consisted of ceftriaxone and gentamicin which was administered to 67.2% (n = 78) and 62.1% (n = 72) of patients, respectively. High rates of antimicrobial resistance could be demonstrated across gram-negative and gram-positive species towards the most common empiric antibiotics. Following the AST results, over 95% (n = 111) of patients required a change of treatment. Our findings demonstrate that current empiric treatment for wound infections is missing its target in hospitalized patients in Kampala. To address the growing problem of AMR in Uganda, there is a pressing need to enhance diagnostic capacity and implement structured antimicrobial stewardship programs.

Divergent Neuroimmune Signatures in the Cerebrospinal Fluid Predict Differential Gender-Specific Survival Among Patients With HIV-Associated Cryptococcal Meningitis.

Survival among people with HIV-associated cryptococcal meningitis (CM) remains low, exceptionally among women with the increased threat of death on current optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system (CNS) prompts a neuroimmune reaction to activate pathogen concomitant factors. However, no consistent diagnostic or prognostic immune-mediated signature is reported to underpin the risk of death or mechanism to improve treatment or survival. We theorized that the distinct neuroimmune cytokine or chemokine signatures in the cerebrospinal fluid (CSF), distinguish survivors from people who died on antifungal treatment, who may benefit from tailored therapy. We considered the baseline clinical disease features, cryptococcal microbiologic factors, and CSF neuroimmune modulated signatures among 419 consenting adults by gender (biological sex assigned at birth) (168 females and 251 males) by 18 weeks of survival on antifungal management. Survival at 18 weeks was inferior among females than males (47% vs. 59%; hazard ratio HR=1.4, 95% CI: 1.0 to 1.9, and p=0.023). Unsupervised principal component analysis (PCA) demonstrated the divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, females displayed lower levels of PD-L1, IL-1RA, and IL-15 than males (all p≤0.028). Female survivors compared with those who died, expressed significant fold elevations in levels of CSF (CCL11 - myeloid and CXCL10 - lymphoid chemokine (in both p=0.001), and CSF Th1, Th2, and Th17 cytokines. In contrast, male survivors expressed distinctly lower levels of CSF IL-15 and IL-8 compared with those who died. Survivors of either gender demonstrated a significant increase in the levels of immune regulatory element, IL-10. In the finale, we classified divergent neuroimmune key signatures in CSF by gender, survival, and intragender-specific survival among people with HIV-associated cryptococcal meningitis. These intragender-specific survival associated-neuroimmune signatures, suggests the discrete role of gender immune regulating mechanisms as the possible targets for interventions to advance therapy to improve survival among people with HIV-associated cryptococcal meningitis.

Investigating One Health risks for human colonisation with extended spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Malawian households: a longitudinal cohort study.

BACKGROUND: Low-income countries have high morbidity and mortality from drug-resistant infections, especially from enteric bacteria such as Escherichia coli. In these settings, sanitation infrastructure is of variable and often inadequate quality, creating risks of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales transmission. We aimed to describe the prevalence, distribution, and risks of ESBL-producing Enterobacterales colonisation in sub-Saharan Africa using a One Health approach. METHODS: Between April 29, 2019, and Dec 3, 2020, we recruited 300 households in Malawi for this longitudinal cohort study: 100 each in urban, peri-urban, and rural settings. All households underwent a baseline visit and 195 were selected for longitudinal follow-up, comprising up to three additional visits over a 6 month period. Data on human health, antibiotic usage, health-seeking behaviours, structural and behavioural environmental health practices, and animal husbandry were captured alongside human, animal, and environmental samples. Microbiological processing determined the presence of ESBL-producing E coli and Klebsiella pneumoniae, and hierarchical logistic regression was performed to evaluate the risks of human ESBL-producing Enterobacterales colonisation. FINDINGS: A paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites. A total of 11 975 samples were cultured, and ESBL-producing Enterobacterales were isolated from 1190 (41·8%) of 2845 samples of human stool, 290 (29·8%) of 973 samples of animal stool, 339 (66·2%) of 512 samples of river water, and 138 (46·0%) of 300 samples of drain water. Multivariable models illustrated that human ESBL-producing E coli colonisation was associated with the wet season (adjusted odds ratio 1·66, 95% credible interval 1·38-2·00), living in urban areas (2·01, 1·26-3·24), advanced age (1·14, 1·05-1·25), and living in households where animals were observed interacting with food (1·62, 1·17-2·28) or kept inside (1·58, 1·00-2·43). Human ESBL-producing K pneumoniae colonisation was associated with the wet season (2·12, 1·63-2·76). INTERPRETATION: There are extremely high levels of ESBL-producing Enterobacterales colonisation in humans and animals and extensive contamination of the wider environment in southern Malawi. Urbanisation and seasonality are key risks for ESBL-producing Enterobacterales colonisation, probably reflecting environmental drivers. Without adequate efforts to improve environmental health, ESBL-producing Enterobacterales transmission is likely to persist in this setting. FUNDING: Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

Mapping hepatitis B virus genotypes on the African continent from 1997 to 2021: a systematic review with meta-analysis.

Hepatitis B virus (HBV) has ten genotypes (A-J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively. These genotypes and sub-genotypes influence the disease prognosis, response to therapy and route of viral transmission. Besides, infection with mixed genotypes and recombinant genotypes has also been reported. This study aimed at mapping the de novo genotypes and correlate them with the immigration trends in order to inform future research on the underlying reasons for the relative distribution of HBV genotypes from a large sample size pooled from many primary studies. Data was extracted from 59 full research articles obtained from Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar. Studies that investigated the genotypes, sub-genotypes, mixed genotypes and recombinant were included. The Z-test and regression were used for the analysis. The study protocol is registered with PROSPERO under the registration number CRD42022300220. Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (P < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern Africa, E in west Africa and D in north Africa (P < 0.0001). Regarding the emerging genotypes B and C on the African continent, genotype B was significantly higher in south Africa than C (P < 0.001). In contrast, genotype C was significantly higher in east Africa than west Africa (P < 0.0001). The A1 and D/E were the most diverse sub-genotypes and genotype mixtures respectively. Finally, we observed a general progressive decrease in the prevalence of predominant genotypes but a progressive increase in the less dominant by region. Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype distribution pattern on the African continent.

Phenotypic Characterization and Antibiograms of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolated at the Human-Animal-Environment Interface Using a One Health Approach Among Households in Wakiso District, Uganda.

Background: The occurrence of extended spectrum beta-lactamase (ESBL) producing bacteria such as Escherichia coli has increasingly become recognized beyond hospital settings. Resistance to other types of antibiotics limits treatment options while the existence of such bacteria among humans, animals, and the environment is suggestive of potential zoonotic and reverse-zoonotic transmission. This study aimed to establish the antibiotic susceptibility profiles of the ESBL-producing Escherichia coli (ESBL-EC) from human, animal, and environmental isolates obtained among farming households within Wakiso district using a One Health approach. Methods: A total of 100 ESBL-EC isolates from humans 35/100 (35%), animals 56/100 (56%), and the environment 9/100 (9%) were tested for susceptibility to 11 antibiotics. This was done using the Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Data were analyzed in STATA ver. 16 and graphs were drawn in Microsoft excel ver. 10. Results: Most of the ESBL-EC isolates (98%) were resistant to more than two antibiotics. ESBL-EC isolates were most susceptible to meropenem (MEM) (88.0%), and imipenem (82.0%) followed by gentamicin (72%). ESBL-EC isolates from humans were most susceptible to meropenem (MEM) followed by imipenem (IPM)> gentamicin (CN)> ciprofloxacin (CIP). Animal samples were more susceptible to MEM, IPM, and CN but were highly resistant to cefotaxime (CTX)> cefepime (FEP)>other antibiotics. Multidrug resistance (MDR) was mostly reported among households keeping goats under intensive husbandry practices. Seven percent of the isolates exhibited carbapenem resistance while 22% showed aminoglycoside resistance. Similar resistance patterns among humans, animals, and environmental samples were also reported. Conclusion: Our study provides baseline information on non-hospital-based MDR caused by ESBL-EC using a One Health approach. ESBL-EC isolates were prevalent among apparently healthy community members, animals, and their environment. It is important to conduct more One Health approach studies to generate evidence on the drivers, resistance patterns, and transmission of ESBL-producing organisms at the human-animal-environmental interface.

Risk Factors, Temporal Dependence, and Seasonality of Human Extended-Spectrum ß-Lactamases-Producing Escherichia coli and Klebsiella pneumoniae Colonization in Malawi: A Longitudinal Model-Based Approach.

BACKGROUND: Sub-Saharan Africa has the highest estimated death rate attributable to antimicrobial resistance, especially from extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E). However, the dynamics of human colonization in the community with ESBL-E are not well described. Inadequate water, sanitation, and hygiene infrastructure and associated behaviors are believed to play an important role in transmission of ESBL-E, and an improved understanding of the temporal dynamics of within-household transmission could help inform the design of future policies. METHODS: In this 18-month study, using microbiological data and household surveys, we built a multivariable hierarchical harmonic logistic regression model to identify risk factors for colonization with ESBL-producing Escherichia coli and Klebsiella pneumoniae, reflecting household structure and temporal correlation of colonization status. RESULTS: Being male was associated with a lower risk of colonization with ESBL-producing E. coli (odds ratio [OR], 0.786; credible interval [CrI], .678-.910), whereas the use of a tube well or a borehole was associated with an increased risk (OR, 1.550; CrI, 1.003-2.394). For ESBL-producing K. pneumoniae, recent antibiotic exposure increased risk of colonization (OR, 1.281; CrI, 1.049-1.565), whereas sharing plates decreased that risk (OR, 0.672; CrI, .460-.980). Finally, the temporal correlation range of 8 to 11 weeks provided evidence that within-household transmission occurs within this time frame. CONCLUSIONS: We describe different risks for colonization with different enteric bacterial species. Our findings suggest interventions to reduce transmission targeted at the household level need to focus on improving water, sanitation, and hygiene infrastructure and associated behaviors, whereas at the community level, they should focus on both environmental hygiene and antibiotic stewardship.

Diarrhoeagenic Escherichia coli isolated from children with acute diarrhoea at Rakai hospital, Southern Uganda.

Background: Diarrhoeagenic Escherichia coli (DEC) is a leading cause of childhood diarrhoea. This study estimated the prevalence of DEC and DEC pathotypes among children with acute diarrhoea in Southern Uganda. Methods: A cross-sectional study was conducted on 267 children less than 5 years with acute diarrhoea, admitted to Rakai General Hospital in Southern Uganda. Faecal samples were collected from the children and processed for isolation of E. coli. The presence of DEC and the distribution of DEC pathotypes were determined by polymerase chain reaction. Results: A total of 102 (38.2%, 102/267) children had DEC of various pathotypes - enteroaggregative E. coli (EAEC) (14.2%); enteropathogenic E. coli (EPEC) (6.7%); enterotoxigenic E. coli (ETEC) (6%); enteroinvasive E. coli (EIEC) (7.5%); enterohemorrhagic E. coli (EHEC) (3%); and cell-detaching E. coli (CDEC) (0.75%). The difference in the overall prevalence of DEC was not significant regarding HIV but individually, EAEC and CDEC were associated with HIV-positive status while ETEC was associated with HIV-negative status. Conclusions: DEC is prevalent in children with acute diarrhoea in Southern Uganda and its identification in children should be considered among strategies for combatting childhood diarrhoea in Africa.

Medical Mycology dissertation topics require prioritisation among Postgraduate Microbiology trainees of Makerere University, Uganda.

Background: As elsewhere worldwide, there is an increasing burden of fungal diseases in Uganda. However, expertise in medical mycology (the study of fungal diseases of medical importance) among clinicians and laboratory personnel remains low. Objective: This study sought to determine the proportion of dissertations on medical mycology among postgraduate medical microbiology trainees at the College of Health Sciences, Makerere University, Uganda. Methods: We retrospectively reviewed the topics of dissertations submitted to the Departments of Medical Microbiology and Immunology & Molecular Biology from 2011 through 2018. The proportion of dissertation topics on medical mycology was analysed using descriptive statistics. Results: A total of 152 dissertations were retrieved. Of these, only 5 (3.3%) were on medical mycology compared to bacteriology (50.7%, n = 77), virology (27.6%, n = 42), parasitology (14.5%, n = 22) and immunology (4.0%, n = 6). Of the 5 dissertations on fungal diseases, the distribution was as follows: cryptococcal meningitis (40%, n = 2), Candidiasis (20%, n = 1), superficial mycoses (20%, n = 1) and other invasive fungal diseases (20%, n = 1). The most common method that was used for studying the fungal diseases was culture 60%, n = 3. Conclusion: There is limited research on medical mycology among the postgraduate medical microbiology trainees of Makerere University, Uganda.

Hepatitis B virus (HBV) serological patterns among the HBsAg negative hospital attendees screened for immunization.

The Hepatitis B virus (HBV) is a highly infectious virus and is endemic in Uganda. It is one of the major etiological agents for liver diseases including liver cancer. In this work, we evaluated the prevalence of the HBV serological markers and the associated socio-demographic factors among hepatitis B surface antigen (HBsAg) seronegative persons screened during routine immunization against the virus in eastern Uganda. Data on the socio-demographic characteristics were collected using a structured questionnaire, while that on the serological markers were obtained from serum samples and evaluated by using the 5-panel HBV One Step Hepatitis B Virus Combo Test Device (FastepR, HBV-P43M). The following markers were evaluated by the panel: HBsAg, HBsAb, HBcAb, and HBeAb. Data were analyzed using SPSS (version 26), and multinomial logistic regression was used to elicit the adjusted odds ratio. All the analysis were performed at a 95% confidence limit, and a P value ≤ 0.05 was considered significant. The 424 participants included in this study were mainly female (62.3%), married (55.4%) and aged 30 years and above (54.2%). The seropositivity of the HBsAb, HBeAb, HBcAb marker prevalence rates was 48(11.3%), 73(17.2%) and 45(10.6%) respectively. The majority of the participants (327, 77.1%) did not present with any marker. Married paricipants were significantly associated with reduced HBsAb seropositvity rate, whereas young people aged 18-29 years were associated the with increased odds of HBsAb seropositivity (p < 0.05). Male participants were significantly associated with the HBeAb and HBcAb seropositivity (p < 0.05). Similarly, contact with an HBV infected person was significantly associated with HBeAb and HBcAb seropositivity (p < 0.05). Further still, blood transfusion was significantly associated with the increased risk of HBcAb seropositivity (P < 0.05). This study has revealed a prevalence of HBV serological markers among the HBsAg seronegative persons in this community and an increased risk of transmission of the virus in the community. Our findings have key consequences pertaining the interventions that are pertinent in the control and prevention of the spread of the virus among apparently health persons.

Soluble Programmed Death-Ligand 1 (sPD-L1) is Elevated in Aggressive Prostate Cancer Disease Among African Men.

INTRODUCTION: Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1)-targeted immunotherapies have become a new mode of treatment for several tumours; however, there is limited evidence on the expression and prognostic value of PD-1/PD-L1 in prostate cancer, especially in African men. METHODS: Plasma concentrations of PD-L1/PD-1 were assessed using enzyme-linked immunosorbent assay in patients with prostate cancer and normal healthy controls at the Uganda Cancer Institute. The associations between plasma PD-L1/PD-1 concentration levels and serum prostate-specific antigen (PSA) levels, Gleason scores, age, and body mass index (BMI) were determined. RESULTS: We found significant differences in the median plasma concentrations of PD-L1 and PD-1 immune checkpoint molecules between prostate cancer cases and normal healthy controls of 0.285 vs 0.035 (p = 0.001) and 0.596 vs 0.355 (p = 0.017), respectively. We found no significant association between age, serum PSA levels, BMI and Gleason scores, and PD-1 among patients with prostate cancer and controls. However, elevated levels of PD-L1 were significantly associated with higher Gleason scores among patients with prostate cancer (p = 0.014). CONCLUSIONS: Elevated PD-L1 levels were statistically significantly linked to high Gleason scores. These results may guide clinicians in assessing the prognosis of patients individually and selecting patients who will be suitable candidates for anti-PD-L1 immunotherapy.

Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. METHODS: A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson's chi-square, multinomial logistic regression, and Mann-Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0.05 was considered statistically significant. RESULTS: Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (p < 0.05). Genotype D was significantly associated with elevated viral load and direct bilirubin (p < 0.05). The recombinant genotype D/E was significantly associated with elevated viral load (p < 0.05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (p < 0.05). CONCLUSION: There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.

IL-6 and IL-8 cytokines are associated with elevated prostate-specific antigen levels among patients with adenocarcinoma of the prostate at the Uganda Cancer Institute.

Background: The possible clinical application of specific cytokines and chemokines contributing to tumorigenesis and the clinical outcome of several cancers has been reported. However, less invasive and easily applicable biomarkers in prostate cancer diagnosis and prognostication are still lacking. This study assessed the levels of plasma cytokines in prostate cancer patients as potential biomarkers for noninvasive early diagnosis. Methods: The plasma levels of nine cytokines, IL-6, IL-8, IL-10, IL-1ß, IL-17A, IL-2, M-CSF, IL-12 and IFN-α, were detected by Luminex© liquid array-based multiplexed immunoassays in 56 prostate cancer patients on androgen deprivation therapy and radiotherapy and 27 normal healthy controls. Results: Levels of plasma proinflammatory cytokines IL-6 and IL-8 were markedly increased in prostate cancer patients compared with controls. There was, however, no significant difference in the concentrations of all cytokines in prostate cancer patients compared with controls. Increasing levels of IL-6 and IL-8 were significantly associated with high levels of plasma prostate-specific antigen (p < 0.05). Conclusion: Proinflammatory cytokines IL-6 and IL-8 are potential biomarkers for prostate cancer pathogenesis and could serve as markers of disease progression.

Microbiological Contamination of Mobile Phones and Mobile Phone Hygiene of Final-Year Medical Students in Uganda: A Need for Educational Intervention.

INTRODUCTION: Contaminated mobile phones act as reservoirs for organisms causing hospital-acquired infections (HAI). Little is known about medical school students' awareness of infection prevention and control (IPC) regarding mobile phone use among medical students. We demonstrated the presence of organisms on mobile phones of final-year medical students at Makerere University College of Health Sciences and evaluated their awareness of IPC regarding mobile phone hygiene and use in a hospital setting. METHODS: In this cross-sectional study, organisms from swabs obtained from 79 medical students' mobile phones were identified and antimicrobial susceptibility test carried out using standard biochemical tests and the automated BD Phoenix instrument. Data were collected using a self-administered questionnaire to assess the students' awareness. The analysis was carried out using STATA software version 16. RESULTS: Seventy (88.6%) mobile phones were contaminated with at least one organism. One hundred forty-eight bacteria were isolated, of which 123 (83.1%) were Gram-positive, 24 (16.2%) were Gram-negative, and 1 (0.7%) was yeast (Candida spp). Coagulase negative staphylococci were the most frequently isolated among Gram-positive bacteria. Acinetobacter baumannii were the most frequently isolated among Gram-negative bacteria. The average IPC practical score regarding mobile phone hygiene (34%) was significantly lower than the average IPC awareness score (77%) (p ≤ 0.0001). Seventy-four (93.7%) students use their phones while rotating in the various wards. Forty (50.6%) of the students cleaned their phones with alcohol-based sanitizer after rotations in the ward. Thirty-five (44.3%) students were aware of IPC programs in the hospital they rotated in. CONCLUSION: There is a high prevalence of bacterial contamination from mobile phones of medical students. The students had lower IPC practical scores compared to IPC awareness scores regarding mobile phone hygiene irrespective of the ward of rotation. Curriculum of final-year medical students should include IPC-related topics, which incorporate practical skills.

Antibiotic Prevalence Study and Factors Influencing Prescription of WHO Watch Category Antibiotic Ceftriaxone in a Tertiary Care Private Not for Profit Hospital in Uganda.

Background: Excessive use of ceftriaxone contributes to the emergence and spread of antimicrobial resistance (AMR). In low and middle-income countries, antibiotics are overused but data on consumption are scarcely available. We aimed to determine the prevalence and factors influencing ceftriaxone prescription in a tertiary care private not-for-profit hospital in Uganda. Methods: A cross-sectional study was carried out from October 2019 through May 2020 at Mengo Hospital in Uganda. Patients admitted to the medical ward and who had been prescribed antibiotics were enrolled. Sociodemographic and clinical data were recorded in a structured questionnaire. Bivariate and adjusted logistic regression analyses were performed to determine factors associated with ceftriaxone prescription. Results: Study participants were mostly female (54.7%). The mean age was 56.2 years (SD: 21.42). The majority (187, 73.3%) presented with fever. Out of the 255 participants included in this study, 129 (50.6%) participants were prescribed ceftriaxone. Sixty-five (25.5%) and forty-one (16.0%) participants had a prescription of levofloxacin and metronidazole, respectively. Seven participants (2.7%) had a prescription of meropenem. Out of 129 ceftriaxone prescriptions, 31 (24.0%) were in combination with other antibiotics. Overall, broad-spectrum antibiotic prescriptions accounted for 216 (84.7%) of all prescriptions. Ceftriaxone was commonly prescribed for pneumonia (40/129, 31%) and sepsis (38/129, 29.5%). Dysuria [OR = 0.233, 95% CI (0.07-0.77), p = 0.017] and prophylactic indication [OR = 7.171, 95% CI (1.36-37.83), p = 0.020] were significantly associated with ceftriaxone prescription. Conclusions: Overall, we observed a high prevalence of prescriptions of ceftriaxone at the medical ward of Mengo Hospital. We recommend an antibiotic stewardship program (ASP) to monitor antibiotic prescription and sensitivity patterns in a bid to curb AMR.

Implementation of the World Health Organization Global Antimicrobial Resistance Surveillance System in Uganda, 2015-2020: Mixed-Methods Study Using National Surveillance Data.

BACKGROUND: Antimicrobial resistance (AMR) is an emerging public health crisis in Uganda. The World Health Organization (WHO) Global Action Plan recommends that countries should develop and implement National Action Plans for AMR. We describe the establishment of the national AMR program in Uganda and present the early microbial sensitivity results from the program. OBJECTIVE: The aim of this study is to describe a national surveillance program that was developed to perform the systematic and continuous collection, analysis, and interpretation of AMR data. METHODS: A systematic qualitative description of the process and progress made in the establishment of the national AMR program is provided, detailing the progress made from 2015 to 2020. This is followed by a report of the findings of the isolates that were collected from AMR surveillance sites. Identification and antimicrobial susceptibility testing (AST) of the bacterial isolates were performed using standard methods at both the surveillance sites and the reference laboratory. RESULTS: Remarkable progress has been achieved in the establishment of the national AMR program, which is guided by the WHO Global Laboratory AMR Surveillance System (GLASS) in Uganda. A functional national coordinating center for AMR has been established with a supporting designated reference laboratory. WHONET software for AMR data management has been installed in the surveillance sites and laboratory staff trained on data quality assurance. Uganda has progressively submitted data to the WHO GLASS reporting system. Of the 19,216 isolates from WHO GLASS priority specimens collected from October 2015 to June 2020, 22.95% (n=4411) had community-acquired infections, 9.46% (n=1818) had hospital-acquired infections, and 68.57% (n=12,987) had infections of unknown origin. The highest proportion of the specimens was blood (12,398/19,216, 64.52%), followed by urine (5278/19,216, 27.47%) and stool (1266/19,216, 6.59%), whereas the lowest proportion was urogenital swabs (274/19,216, 1.4%). The mean age was 19.1 (SD 19.8 years), whereas the median age was 13 years (IQR 28). Approximately 49.13% (9440/19,216) of the participants were female and 50.51% (9706/19,216) were male. Participants with community-acquired infections were older (mean age 28, SD 18.6 years; median age 26, IQR 20.5 years) than those with hospital-acquired infections (mean age 17.3, SD 20.9 years; median age 8, IQR 26 years). All gram-negative (Escherichia coli, Klebsiella pneumoniae, and Neisseria gonorrhoeae) and gram-positive (Staphylococcus aureus and Enterococcus sp) bacteria with AST showed resistance to each of the tested antibiotics. CONCLUSIONS: Uganda is the first African country to implement a structured national AMR surveillance program in alignment with the WHO GLASS. The reported AST data indicate very high resistance to the recommended and prescribed antibiotics for treatment of infections. More effort is required regarding quality assurance of laboratory testing methodologies to ensure optimal adherence to WHO GLASS-recommended pathogen-antimicrobial combinations. The current AMR data will inform the development of treatment algorithms and clinical guidelines.

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%), 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.