| 1. |
- Marwa, Karol J., et al.
(författare)
-
Artemether-lumefantrine and dihydroartemisinin-piperaquine treatment outcomes among children infected with uncomplicated Plasmodium falciparum malaria in Mwanza,Tanzania
- 2021
-
Ingår i: Tropical Medicine and Health. - : Springer Nature. - 1348-8945 .- 1349-4147. ; 49
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Artemisinin based combination therapies (ACTs) have been a cornerstone in the treatment of malaria in the world. A rapid decline in dihydroartemisinin piperaquine (DHP) and artemether lumefantrine (ALU) efficacies has been reported in some parts of South East Asia, the historical epicenter for the antimalarial drug resistance. Prolonged drug use is associated with selection of resistant parasites due to exposure to inadequate drug levels hence effects on treatment outcomes in malaria. ALU and DHP are used as first line and alternative first line, respectively, in Tanzania. This study was carried in lgombe, Tanzania to assess the efficacies of ALU and DHP in routine treatment of uncomplicated malaria among children.Methods: This was a prospective study involving children up to 10 years and followed up for 28 and 35 days as per the WHO protocol, 2015 for monitoring antimalarial drug efficacy. The primary end points were crude and adjusted Adequate Clinical and Parasitological Response (ACPR), parasite clearance rate and reported adverse events.Results: A total of 205 children with uncomplicated malaria were enrolled. One hundred and sixteen participants were treated with ALU, while 89 participants were treated with DHP. Two participants in the ALU group were lost within the 24 h of follow-up. The PCR unadjusted ACPR was 108 (94.7%) for ALU and 88 (98.9%) for DHP, while the PCR adjusted ACPR was 109(95.6%) and 88(98.9%) for ALU and DHP, respectively, at 28 day follow-up. No treatment failure was observed in both groups. Cumulative risk of recurrent parasitemia was similar in both groups (p = 0.32). Age and parasite density were strong predictors for persistent day 1 parasitemia (p = 0.034 and 0.026, respectively). Nausea and vomiting, abdominal pain and headache were the most clinical adverse events reported in both groups of patients.Conclusion: The present study shows that ALU and DHP are still efficacious after more than a decade of use with PCR corrected efficacies greater than 95% implying a failure rate less than 5% which is below the WHO minimum threshold requirement for recommendation of a change in the treatment policy. Both drugs were well tolerated with no major adverse events reported.
|
|
| 2. |
- Marwa, Karol J., et al.
(författare)
-
Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population : a concern about the metabolism of artemisinin-based combinations
- 2014
-
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 13, s. 420-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Artemisinin-based combinations currently recommended for treatment of uncomplicated Plasmodium falciparum malaria in many countries of sub-Saharan Africa are substrates of CYP enzymes. The cytochrome enzyme system is responsible for metabolism of about 80-90% of clinically used drugs. It is, therefore, important to obtain the pharmacogenetics of the population in the region with respect to these combinations and thereby enable practitioners to predict treatment outcomes. The aim of this study was to detect and determine allelic frequencies of CYP2C8*2, CYP2C8*3, CYP3A4*1B, CYP3A5*3 and CYP2B6*6 variant alleles in a Tanzanian indigenous population. Methods: Genomic DNA extraction from blood obtained from 256 participants who escorted patients at Karume Health Centre in Mwanza Tanzania, was carried out using the Gene JET (TM) Genomic DNA purification kit (Thermo Scientific). Genotyping for the cytochrome P450 variant alleles was performed using predesigned primers. Amplification was done by PCR while differentiation between alleles was done by restriction fragment length polymorphism (PCR-RFLP) (for CYP2C8*2, CYP2C8*3) and sequencing (for CYP2B6*6, CYP3A5*3 and CYP3A4*1B). Results: CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively. Conclusion: Prevalence of CYP2C8*2, CYP3A5*3, CYP3A4*1B and CYP2B6*6 mutations in a Tanzanian population/ subjects are common. The impact of these point mutations on the metabolism of anti-malarial drugs, particularly artemisinin-based combinations, and their potential drug-drug interactions (DDIs) needs to be further evaluated.
|
|
| 3. |
- Marwa, Karol J., et al.
(författare)
-
Lumefantrine plasma concentrations in uncontrolled conditions among patients treated with artemether-lumefantrine for uncomplicated plasmodium falciparum malaria in Mwanza, Tanzania
- 2022
-
Ingår i: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 123, s. 192-199
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic efficacy of artemether-lumefantrine is highly dependent on adequate systemic exposure to the partner drug lumefantrine particularly day 7 lumefantrine plasma concentration. There has been contradicting findings on the role of the cut-off values in predicting treatment outcomes among malaria patients in malaria endemic regions. This study assesses the day 3 and 7 lumefantrine plasma concentrations including related determinant factors and their influence on treatment outcomes among treated Tanzanian children and adults in uncontrolled conditions (real life condition).Methods: Data was nested from an efficacy study employing the WHO protocol, 2015 for monitoring antimalarial drug efficacy. Lumefantrine plasma concentration was measured by high performance liquid chromatography with ultraviolet (HPLC-UV).Results: Lumefantrine plasma concentrations below 175ng/ml and 20 0ng/ml on day 3 and 7 did not affect adequate clinical and parasitological response (ACPR) and recurrence of infection ( p = 0.428 and 0.239 respectively). Age and baseline parasitemia were not as-sociated to day 3 median lumefantrine plasma concentrations (p = 0.08 and 0.31 respectively) and day 7 lumefantrine plasma concentrations (p = 0.07 and 0.41 respectively). However, the day 3 and day 7 lumefantrine plasma concentrations were significantly higher in males compared to females ( p = 0.03 and 0.042 respectively).Conclusion: Lumefantrine plasma concentrations below cut-off points (175ng/ml and 20 0ng/ml) on day 3 and 7 did not influence treatment outcomes.
|
|
| 4. |
- Marwa, Karol J., et al.
(författare)
-
Plasmodium falciparum Merozoite Surface Proteins Polymorphisms and Treatment Outcomes among Patients with Uncomplicated Malaria in Mwanza, Tanzania
- 2022
-
Ingår i: Journal of Tropical Medicine. - : HINDAWI LTD. - 1687-9686 .- 1687-9694. ; 2022
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The severity of malaria infection depends on the host, parasite and environmental factors. Merozoite surface protein (msp) diversity determines transmission dynamics, P. falciparum immunity evasion, and pathogenesis or virulence. There is limited updated information on P. falciparum msp polymorphisms and their impact on artemether-lumefantrine treatment outcomes in Tanzania. Therefore, this study is aimed at examining msp genetic diversity and multiplicity of infection (MOI) among P. falciparum malaria patients. The influence of MOI on peripheral parasite clearance and adequate clinical and parasitological response (ACPR) was also assessed. Methods. Parasite DNA was extracted from dried blood spots according to the manufacture's protocol. Primary and nested PCR were performed. The PCR products for both the block 2 region of msp1 and the block 3 regions of msp2 genes and their specific allelic families were visualized on a 2.5% agarose gel. Results. The majority of the isolates, 58/102 (58.8%) for msp1 and 69/115 (60.1%) for msp2, harboured more than one parasite genotypes. For the msp1 gene, K1 was the predominant allele observed (75.64%), whereas R033 occurred at the lowest frequency (43.6%). For the msp2 gene, the 3D7 allele was observed at a higher frequency (81.7%) than the FC27 allele (76.9%). The MOIs were 2.44 for msp1 and 2.27 for msp2 (p = 0.669). A significant correlation between age and multiplicity of infection (MOI) for msp1 or MOI for msp2 was not established in this study (rho = 0.074, p = 0.521 and rho = -0.129, p = 0.261, respectively). Similarly, there was no positive correlation between parasite density at day 1 and MOI for both msp1 (rho = 0.113, p = 0.244) and msp2 (rho = 0.043, p = 0.712). The association between MOI and ACPR was not observed for either msp1 or mps2 (p = 0.776 and 0.296, respectively). Conclusions. This study reports high polyclonal infections, MOI and allelic frequencies for both msp1 and msp2. There was a lack of correlation between MOI and ACPR. However, a borderline significant correlation was observed between day 2 parasitaemia and MOI.
|
|
| 5. |
- Marwa, Karol J., et al.
(författare)
-
The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa : A Systematic Review
- 2023
-
Ingår i: Pharmacogenomics and Personalized Medicine. - : Dove Medical Press. - 1178-7066. ; 16, s. 449-461
-
Forskningsöversikt (refereegranskat)abstract
- Background: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations.Methods: Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies.Results: Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles.Conclusion: This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among P. falciparum malaria patients.
|
|
