Professor
Pauline Byakika-Kibwika
Current Organisation
Infectious Diseases Institute Limited (IDI)
Current Job Title
Biography
Publications
BACKGROUND:
Malaria control largely depends on availability of highly efficacious drugs, however, over the years, has been threatened by emergence of drug resistance. It is, therefore, important to monitor the impact of recurrent anti-malarial treatment on the long-term efficacy of anti-malarial regimens, especially in sub-Saharan African countries with high malaria transmission. Evaluation of parasite clearance following treatment of severe malaria with intravenous artesunate among patients in Eastern Uganda, was performed, as a contribution to monitoring anti-malarial effectiveness.
METHODS:
Parasite clearance data obtained from a clinical trial whose objective was to evaluate the 42-day parasitological treatment outcomes and safety following treatment of severe malaria with intravenous artesunate plus artemisinin-based combination therapy among patients attending Tororo District Hospital in Eastern Uganda, were analysed. Serial blood smears were performed at 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 h, followed by 6-hourly blood smears post start of treatment until 6 h post the first negative blood smear when parasite clearance was achieved. Study endpoints were; parasite clearance half-life (the time required for parasitaemia to decrease by 50% based on the linear portion of the parasite clearance slope) and parasite clearance time (time required for complete clearance of initial parasitaemia).
RESULTS:
One hundred and fifty participants with severe malaria were enrolled. All participants were treated with intravenous artesunate. All study participants tolerated artesunate well with rapid recovery from symptoms and ability to take oral mediation within 24 h. No immediate adverse events were recorded. The median (IQR) number of days to complete parasite clearance was of 2 (1-2). The median (IQR) time to clear 50% and 99% parasites was 4.8 (3.61-7.10) and 17.55 (14.66-20.66) h, respectively. The median estimated clearance rate constant per hour was 0.32. The median (IQR) slope half-life was 2.15 (1.64, 2.61) h.
CONCLUSION:
Parasite clearance following treatment with intravenous artesunate was rapid and adequate. This finding provides supportive evidence that resistance to artemisinins is unlikely to have emerged in this study area. Continuous monitoring of artemisinin effectiveness for malaria treatment should be established in high malaria transmission areas in sub-Saharan Africa where spread of resistance would be disastrous. Trial registration The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011, http://www.pactr.org/ ).
OBJECTIVE:
To determine the prevalence and factors associated with dyslipidaemias in women using hormonal contraceptives.
DESIGN:
Cross-sectional study SETTING: Mulago Hospital, Kampala, Uganda PARTICIPANTS: Three hundred and eighty-four consenting women, aged 18-49 years, who had used hormonal contraceptives for at least 3 months prior to the study.
STUDY OUTCOME:
Dyslipidaemias (defined as derangements in lipid profile levels which included total cholesterol ≥200 mg/dL, high-density lipoprotein <40 mg/dL, triglyceride >150 mg/dL or low-density lipoprotein ≥160 mg/dL) for which the prevalence and associated factors were obtained.
RESULTS:
The prevalence of dyslipidaemias was 63.3% (95% CI: 58.4 to 68.1). Body mass index (BMI) (PR=1.33, 95% CI: 1.15 to 1.54, p<0.001) and use of antiretroviral therapy (ART) (PR=1.21, 95% CI: 1.03 to 1.42, p=0.020) were the factors significantly associated with dyslipidaemias.
CONCLUSION:
Dyslipidaemias were present in more than half the participants, and this puts them at risk for cardiovascular diseases. The high-risk groups were women with a BMI greater than 25 Kg/m2 and those who were on ART. Therefore, lipid profiles should be assessed in women using hormonal contraceptives in order to manage them better.
Across sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artemether-lumefantrine or artesunate-amodiaquine given with 50 mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artemether-lumefantrine or artesunate-amodiaquine and dolutegravir. The dolutegravir/artemether-lumefantrine interaction was evaluated in a two-way crossover study and measured artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine over 264 h. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, and desethylamodiaquine over 624 h. Noncompartmental analysis was performed, and geometric mean ratios and 90% confidence intervals were generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, the time to maximum concentration, and the area under the concentration-time curve (AUC) for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine, nor did it significantly alter the AUC for artesunate, dihydroartemisinin, amodiaquine, and desethylamodiaquine. Coadministration of dolutegravir with artemether-lumefantrine resulted in a 37% decrease in DTG trough concentrations. Coadministration of dolutegravir with artesunate-amodiaquine resulted in 42 and 24% approximate decreases in the DTG trough concentrations and the AUC, respectively. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and dolutegravir exposure with artesunate-amodiaquine are unlikely to be of clinical significance since the DTG trough concentrations were above dolutegravir target concentrations of 300 ng/ml. Study drugs were well tolerated with no serious adverse events. Standard doses of artemether-lumefantrine and artesunate-amodiaquine should be used in patients receiving dolutegravir. (This study has been registered at ClinicalTrials.gov under identifier NCT02242799.).
Copyright © 2019
Project Title
Optimizing Malaria Treatment for HIV-Malaria co-infected Individuals by Addressing Drug Interactions between Artemisinin-based Combination Therapies and Antiretroviral Drugs (OPTIMAL)
EDCTP Project
TMA2017SF-1943
EDCTP Program
EDCTP2
EDCTP Project Call
Senior Fellowship (SF)
Host Organisation
| Department | Institution | Country |
|---|---|---|
| Infectious Diseases Institute Limited (IDI) | UG |
Project Objectives
General Objective: To utilize innovative interventions to overcome drug interactions between artemether-lumefantrine and efavirenz to guide malaria treatment for individuals co-infected with HIV and malaria Specific Objectives 1. To determine the safety and Pharmacokinetics of the double dose artemether-lumefantrine when administered to healthy volunteers (malaria negative and HIV negative individuals). 2. To determine the safety and Pharmacokinetics of the 5-day course of artemether-lumefantrine when administered to healthy volunteers (malaria negative and HIV negative individuals). 3. To determine the safety, pharmacokinetics, and malaria treatment outcome of a standard dose of artemether-lumefantrine compared to double of the standard dose for weight and a 5-day course of artemether-lumefantrine for treatment of uncomplicated malaria among HIV-Malaria co-infected individuals receiving efavirenz (400mg) based ART. 4. To determine the safety, Pharmacokinetics, and malaria treatment outcome of artemether-lumefantrine when administered with Dolutegravir based ART among HIV-malaria co-infected individuals.
Study Design
Randomised Clinical and Pharmacokinetic Trial
Project Summary
To train and conduct a Randomised Clinical and Pharmacokinetic Trial to generate data to optimize malaria treatment for individuals co-infected with HIV and malaria, by utilizing innovative interventions to overcome the significant drug interactions between artemether-lumefantrine and efavirenz.
Results & Outcomes
Project Title
Comparison of efficacy, safety and pharmacokinetics of intravenous artesunate and intravenous quinine followed by oral artemisinin combination therapy for severe malaria treatment in Uganda AND evaluation of pharmacokinetic drug interactions of artesunate, quinine, lumefantrine and piperaquine with antiretroviral drugs
EDCTP Project
TA.2009.40200.020
EDCTP Program
EDCTP1
EDCTP Project Call
Senior Fellowship (SF)
Host Organisation
| Department | Institution | Country |
|---|---|---|
| Infectious Diseases Institute | Makerere University College Of Health Sciences | UG |
| Medicine | Makerere University | UG |
Project Objectives
To evaluate the effectiveness of IV artesunate plus ACT and IV quinine plus ACT as well as to study the pharmacokinetics of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treatment of severe malaria in adults and children in Tororo district hospital, Uganda. 1. To compare treatment outcome (measured as risk of recurrent parasitaemia and risk of recurrent symptomatic malaria) following treatment with IV quinine followed by oral ACT (Artemether-Lumefantrine or Dihydroartemisinin-piperaquine) and IV artesunate followed by oral ACT (AL or DP) for treatment of severe malaria in Ugandan patients 2. To compare parasite clearance time following treatment with IV quinine followed by oral ACT (AL or DP) and IV artesunate followed by oral ACT (AL or DP) for treatment of severe malaria in Ugandan patients 3. To investigate the pharmacokinetic parameters of IV quinine, IV artesunate, oral AL and oral DP during severe malaria treatment in Ugandan patients and correlate these with treatment outcome 4. To investigate the pharmacokinetic drug interactions of quinine, artesunate, lumefantrine and piperaquine with the antiretroviral drugs (Nevirapine, Efavirenz, Lopinavir/ritonavir) in Ugandan patients.
Study Design
PK and drug interaction studies