Browsing by Author "Mayito, Jonathan"
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Item Drug–drug interactions between antiretrovirals and drugs used in the management of neglected tropical diseases: important considerations in the WHO 2020 Roadmap and London Declaration on Neglected Tropical Diseases(Lippincott Williams & Wilkins, 2020) Sedena, Kay; Khooa, Saye; Backa, David; Prevattb, Natalie; Lamorde, Mohammed; Byakika-Kibwika, Pauline; Mayito, Jonathan; Ryan, Mairin; Merry, ConceptaTheWHO2020 Roadmap on neglected tropical diseases (NTDs) and the 2012 London Declaration on NTDs aim to ‘enable more than a billion people suffering from neglected tropical diseases to lead healthier and more productive lives’ and ‘chart a new course towards health and sustainability’. Two out of the five strategies for the prevention, control, elimination and eradication of NTDs set out in the WHO 2020 Roadmap involve sustaining and expanding existing drug donation programs to meet demand through to 2020. To this end, the governments of the US, UK and United Arab Emirates, theWorld Bank and the Bill and Melinda Gates Foundation along with 13 pharmaceutical companies, have announced the largest collaborative effort to date to combat NTDs.Item Implementation of the World Health Organization Global Antimicrobial Resistance Surveillance System in Uganda, 2015-2020: Mixed-Methods Study Using National Surveillance Data(JMIR public health and surveillance, 2021) Nabadda, Susan; Kakooza, Francis; Kiggundu, Reuben; Walwema, Richard; Bazira, Joel; Mayito, Jonathan; Mugerwa, Ibrahimm; Sekamatte, Musa; Kambugu, Andrew; Lamorde, Mohammed; Kajumbula, Henry; Mwebasa, HenryAntimicrobial 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.Item Lower artemether, dihydroartemisinin and lumefantrine concentrations during rifampicin-based tuberculosis treatment(Lippincott Williams & Wilkins, 2013) Lamorde, Mohammed; Byakika-Kibwika, Pauline; Mayito, Jonathan; Nabukeera, Lillian; Ryan, Mairin; Hanpithakpong, Warunee; Lefe`vree, Gilbert; Backf, David J.; Khoof, Saye H.; Merry, ConceptaMalaria and tuberculosis (TB) are co-endemic in many parts of the developing world. Although malaria transmission may occur throughout the duration of TB treatment, drug data between antimalarial drugs and anti- TB drugs are limited [1]. The WHO recommends artemisinin combination therapies (ACTs) for uncomplicated malaria caused by Plasmodium falciparum, whereas for TB treatment, the WHO recommends rifampicinbased therapy [2,3]. However, no data exist on drug interactions between ACTs and rifampicin-based TB treatment.Item Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults(Malaria Journal, 2012) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Mayito, Jonathan; Nabukeera, Lillian; Mayanja-Kizza, Harriet; Katabira, Elly; Hanpithakpong, Warunee; Obua, Celestino; Pakker, Nadine; Lindegardh, Niklas; Tarning, Joel; de Vries, Peter J.; Merry, ConceptaSevere malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria. Methods: Fourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134).Item Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults(Journal of Antimicrobial Chemotherapy, 2012) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Mayito, Jonathan; Nabukeera, Lillian; Namakula, Rhoda; Mayanja-Kizza, Harriet; Katabira, Elly; Ntale, Muhammad; Pakker, Nadine; Ryan, Mairin; Hanpithakpong, Warunee; Tarning, Joel; Lindegardh, Niklas; Vries, Peter J. de; Khoo, Saye; Back, DavidCo-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug–drug interactions between artemether/lumefantrine and efavirenz or nevirapine. Methods: We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/ lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared.Item Steady-state pharmacokinetics of lopinavir plus ritonavir when administered under different meal conditions in HIV-infected Ugandan adults(Journal of acquired immune deficiency syndromes, 2012) Lamorde, Mohammed; Byakika-Kibwika, Pauline; Boffito, Marta; Nabukeera, Lillian; Mayito, Jonathan; Ogwal- Okeng, Jasper; Tjia, John; Back, David; Khoo, Saye; Ryan, Mairin; Merry, ConceptaWe investigated the effect of food on the steady-state pharmacokinetics of lopinavir and ritonavir in 12 Ugandan patients receiving lopinavir co-formulated with ritonavir (LPV/r) tablets using a cross-over design. Intensive pharmacokinetic sampling was performed seven days apart following LPV/r dosing under moderate fat, high fat and fasted meal conditions. Lopinavir and ritonavir concentrations were determined by liquid chromatography and tandem mass spectrometry. Compared to the fasted state, a high fat meal reduced lopinavir and ritonavir area under the curve (AUC) by 14% and 29%, respectively. With a moderate fat meal, AUC for both drugs was similar to the fasted state.