Browsing by Author "Mande, Emmanuel"

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    Antibiotic overuse, poor antimicrobial stewardship, and low specificity of syndromic case management in a cross section of men with urethral discharge syndrome in Kampala, Uganda
    (PLoS ONE, 2024) Hamill, Matthew M.; Onzia, Annet; Rosalind, M. Parkes-Ratanshi; Kyambadde, Peter; Mande, Emmanuel; Nakate, Vivian; Johan, H. Melendez; Ethan, Gough; Manabe, Yukari C.
    Objective High prevalence of sexually transmitted infections (STIs) combined with poor antimicrobial stewardship are drivers of STI antimicrobial resistance (AMR) especially in resource-limited settings where syndromic case management (SCM) is the norm. We characterized patterns of antibiotic use prior to clinic attendance and study enrollment in Ugandan men with urethral discharge syndrome (UDS), evaluated in-clinic prescribing, and the performance characteristics of SCM. Methods Participants were recruited from government clinics participating in an existing gonococcal surveillance program in Kampala, Uganda. Questionnaires including antimicrobial use prior to attendance, prior episodes of UDS, penile swabs, and blood samples were collected. Bivariable and multivariable logistic regression models were used to estimate odds ratios (OR) for preselected factors likely to be associated with antibiotic use. In-clinic antibiotic treatment data were extracted from clinical notes, and the performance of SCM against laboratory-based STI diagnoses was evaluated. Findings Between October 2019 and November 2020, 100(40%) of 250 men with UDS reported taking antibiotics in the 14days prior to attending the clinic. Of these 210(84%) had at least one curable STI and 20% had a reactive point-of-care HIV test. Multivariable analysis demonstrated significant associations between recent antimicrobial use and duration of UDS symptoms <6 days (OR 2.98(95%CI 1.07,8.36), p = 0.038), and sex with women only (OR 0.08(95%CI 0.01,0.82),p = 0.038). The sensitivity of SCM ranged from 80.0% to 94.4%; specificity was low between 5.6% and 33.1%. The positive predictive value of SCM ranged from 2.4(95%CI 0.7,6.0) for trichomoniasis to 63.4(95%CI 56.5,69.9) for gonorrhea. Conclusion Pre-enrollment antibiotic use was common in this population at high risk of STI and HIV. Combined with the poor specificity of SCM for male UDS, extensive antibiotic use is a likely driver of STI-AMR in Ugandan men. Interventions to improve antimicrobial stewardship and deliver affordable diagnostics to augment SCM and decrease overtreatment of STI syndromes are required.
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    Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda
    (African Journal of Laboratory Medicine, 2023) Omali, Denis; Buzibye, Allan; Kwizera, Richard; Byakika-Kibwika, Pauline; Namakula, Rhoda; Matovu, Joshua; Mbabazi, Olive; Mande, Emmanuel; Sekaggya-Wiltshire, Christine; Nakanjako, Damalie; Gutteck, Ursula; McAdam, Keith; Easterbrook, Philippa; Kambugu, Andrew; Fehr, Jan; Castelnuovo, Barbara; Manabe, Yukari C.; Lamorde, Mohammed; Mueller, Daniel; Merry, Concepta
    Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. Intervention: Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. Lessons learnt: Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. Recommendations: Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries.
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    A Portable Magnetofluidic Platform for Detecting Sexually Transmitted Infections and Antimicrobial Susceptibility
    (Science translational medicine, 2021) Trick, Alexander Y.; Melendez, Johan H.; Onzia, Annet; Zawedde, Aidah; Nakku-Joloba, Edith; Kyambadde, Peter; Mande, Emmanuel; Matovu, Joshua; Atuheirwe, Maxine; Kwizera, Richard
    Effective treatment of sexually transmitted infections (STIs) is limited by diagnostics that cannot deliver results rapidly while the patient is still in the clinic. The gold standard methods for identification of STIs are nucleic acid amplification tests (NAATs), which are too expensive for widespread use and have lengthy turnaround times. To address the need for fast and affordable diagnostics, we have developed a portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) polymerase chain reaction (PCR) test. We show that it can detect Neisseria gonorrhoeae, the pathogen causing gonorrhea, with simultaneous genotyping of the pathogen for resistance to the antimicrobial drug ciprofloxacin in <15 min. The duplex test was integrated into a low-cost thermoplastic cartridge with automated processing of penile swab samples from patients using magnetic beads. A compact instrument conducted DNA extraction, PCR, and analysis of results while relaying data to the user via a smartphone app. This platform was tested on penile swab samples from sexual health clinics in Baltimore, MD, USA (n = 66) and Kampala, Uganda (n = 151) with an overall sensitivity and specificity of 97.7% (95% CI, 94.7 to 100%) and 97.6% (95% CI, 94.1 to 100%), respectively, for N. gonorrhoeae detection and 100% concordance with culture results for ciprofloxacin resistance. This study paves the way for delivering accessible PCR diagnostics for rapidly detecting STIs at the point of care, helping to guide treatment decisions and combat the rise of antimicrobial resistant pathogens.
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    Translational Research in Uganda: Linking Basic Science to Bedside Medicine in a Resource Limited Setting
    (Journal of translational medicine, 2021) Kwizera, Richard; Mande, Emmanuel; Omali, Denis; Okurut, Samuel; Nabweyambo, Sheila; Nabatanzi, Rose; Nakanjako, Damalie; Meya, David B.
    Translational research is a process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs. Translational research is less explored in the Ugandan health system, yet, it is fundamental in enhancing human health and well-being. With the current high disease burden in Uganda, there are many opportunities for exploring, developing and utilising translational research. In this article, we described the current state, barriers and opportunities for translational research in Uganda. We noted that translational research is underutilised and hindered by limited funding, collaborations, laboratory infrastructure, trained personnel, equipment and research diversity. However, with active collaborations and funding, it is possible to set up and develop thriving translational research in Uganda. Researchers need to leverage existing international collaborations to enhance translational research capacity development. Expanding the integration of clinical and translational research in Uganda health care system will improve clinical care.