19 results on '"Minzi, Omary M. S."'
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2. Electrolytes supplementation can decrease the risk of nephrotoxicity in patients with solid tumors undergoing chemotherapy with cisplatin
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Minzi, Omary M. S., Lyimo, Tatu E., Furia, Francis F., Marealle, Alphonce I., Kilonzi, Manase, Bwire, George M., and Malichewe, Christina
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- 2020
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3. Adoption of the new antimalarial drug policy in Tanzania – a cross-sectional study in the community
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Eriksen, Jaran, Nsimba, Stephen E. D., Minzi, Omary M. S., Sanga, Anku J., Petzold, Max, Gustafsson, Lars L., Warsame, Marian Y., and Tomson, Göran
- Published
- 2005
4. Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women
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Mutagonda, Ritah F., primary, Kamuhabwa, Appolinary A. R., additional, Minzi, Omary M. S., additional, Massawe, Siriel N., additional, Asghar, Muhammad, additional, Homann, Manijeh V., additional, Färnert, Anna, additional, and Aklillu, Eleni, additional
- Published
- 2017
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5. Malaria prevalence, severity and treatment outcome in relation to day 7 lumefantrine plasma concentration in pregnant women
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Mutagonda, Ritah F., primary, Kamuhabwa, Appolinary A. R., additional, Minzi, Omary M. S., additional, Massawe, Siriel N., additional, Maganda, Betty A., additional, and Aklillu, Eleni, additional
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- 2016
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6. Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population : a concern about the metabolism of artemisinin-based combinations
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Marwa, Karol J., Schmidt, Theresa, Sjögren, Maria, Minzi, Omary M. S., Kamugisha, Erasmus, Swedberg, Göte, Marwa, Karol J., Schmidt, Theresa, Sjögren, Maria, Minzi, Omary M. S., Kamugisha, Erasmus, and Swedberg, Göte
- 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.
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- 2014
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7. The influence of nevirapine and efavirenz-based anti-retroviral therapy on the pharmacokinetics of lumefantrine and anti-malarial dose recommendation in HIV-malaria co-treatment.
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Maganda, Betty A., Ngaimisi, Eliford, Kamuhabwa, Appolinary A. R., Aklillu, Eleni, and Minzi, Omary M. S.
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NEVIRAPINE ,EFAVIRENZ ,DRUG therapy for malaria ,MALARIA treatment ,ANTIRETROVIRAL agents ,PHARMACOKINETICS ,ANTIMALARIALS - Abstract
Background: HIV-malaria co-infected patients in most parts of sub-Saharan Africa are treated with both artemether-lumefantrine (AL) and efavirenz (EFV) or nevirapine (NVP)-based antiretroviral therapy (ART). EFV, NVP, artemether and lumefantrine are substrates, inhibitors or inducers of CYP3A4 and CYP2B6, creating a potential for drug-drug interactions. The effect of EFV and/or NVP on lumefantrine pharmacokinetic profile among HIV-malaria co-infected patients on ART and treated with AL was investigated. Optimal lumefantrine dosage regimen for patients on EFV-based ART was determined by population pharmacokinetics and simulation. Methods: This was a non-randomized, open label, parallel, prospective cohort study in which 128, 66 and 75 HIV-malaria co-infected patients on NVP-based ART (NVP-arm), EFV-based ART (EFV-arm) and ART naïve (control-am) were enrolled, respectively. Patients were treated with AL and contributed sparse venous plasma samples. Pharmacokinetic analysis of lumefantrine was done using non-linear mixed effect modelling. Results: Of the evaluated models, a two-compartment pharmacokinetic model with first order absorption and lag-time described well lumefantrine plasma concentrations time profile. Patients in the EFV-arm but not in the NVP-arm had significantly lower lumefantrine bioavailability compared to that in the control-arm. Equally, 32% of patients in the EFV-arm had day-7 lumefantrine plasma concentrations below 280 ng/ml compared to only 4% in the control-arm and 3% in the NVP-arm. Upon post hoc simulation of lumefantrine exposure, patients in the EFV-arm had lower exposure (median (IQR)) compared to that in the control-arm; AUC
0-inf ; was 303,130 (211,080-431,962) versus 784,830 (547,405-1,116,250); day-7 lumefantrine plasma concentrations was: 335.5 (215.8-519.5) versus 858.7 (562.3-1,333.8), respectively. The predictive model through simulation of lumefantrine exposure at different dosage regimen scenarios for patients on EFV-based ART, suggest that AL taken twice daily for five days using the current dose could improve lumefantrine exposure and consequently malaria treatment outcomes. Conclusions: Co-treatment of AL with EFV-based ART but not NVP-based ART significantly reduces lumefantrine bioavailability and consequently total exposure. To ensure adequate lumefantrine exposure and malaria treatment success in HIV-malaria co-infected patients on EFV-based ART, an extension of the duration of AL treatment to five days using the current dose is proposed. [ABSTRACT FROM AUTHOR]- Published
- 2015
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8. Existence of antimalarial formulations with low bioavailability in Tanzania
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Minzi, Omary M S, primary, Massele, Amosy, additional, Justin-Temu, Mary, additional, Ericsson, Örjan, additional, and Gustafsson, Lars L, additional
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- 2006
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9. Outcome of artemether-lumefantrine treatment for uncomplicated malaria in HIV-infected adult patients on anti-retroviral therapy.
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Maganda, Betty A., Minzi, Omary M. S., Kamuhabwa, Appolinary A. R., Ngasala, Billy, and Sasi, Philip G.
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MALARIA treatment , *HIV infections , *THERAPEUTICS , *ANTIMALARIALS , *NON-nucleoside reverse transcriptase inhibitors , *PARASITOLOGY - Abstract
Background Malaria and HIV infections are both highly prevalent in sub-Saharan Africa, with HIVinfected patients being at higher risks of acquiring malaria. The majority of antiretroviral (ART) and anti-malarial drugs are metabolized by the CYP450 system, creating a chance of drug-drug interaction upon co-administration. Limited data are available on the effectiveness of the artemether-lumefantrine combination (AL) when co-administered with non-nucleoside reverse transcriptase inhibitors (NNRTIs). The aim of this study was to compare anti-malarial treatment responses between HIV-1 infected patients on either nevirapine- or efavirenz-based treatment and those not yet on ART (control-arm) with uncomplicated falciparum malaria, treated with AL. Method This was a prospective, non-randomized, open-label study conducted in Bagamoyo district, with three arms of HIV-infected adults: efavirenz-based treatment arm (EFV-arm) n = 66, nevirapine-based treatment arm (NVP-arm) n = 128, and control-arm n = 75, with uncomplicated malaria. All patients were treated with AL and followed up for 28 days. The primary outcome measure was an adequate clinical and parasitological response (ACPR) after treatment with AL by day 28. Results Day 28 ACPR was 97.6%, 82.5% and 94.5% for the NVP-arm, EFV-arm and control-arm, respectively. No early treatment or late parasitological failure was reported. The cumulative risk of recurrent parasitaemia was >19-fold higher in the EFV-arm than in the control-arm (Hazard ratio [HR], 19.11 [95% confidence interval {CI}, 10.5-34.5]; P < 0.01). The cumulative risk of recurrent parasitaemia in the NVP-arm was not significantly higher than in the control-arm ([HR], 2.44 [95% {CI}, 0.79-7.6]; P = 0.53). The median (IQR) day 7 plasma concentrations of lumefantrine for the three arms were: 1,125 ng/m (638.8-1913), 300.4 ng/ml (220.8-343.1) and 970 ng/ml (562.1-1729) for the NVP-arm, the EFV-arm and the control-arm, respectively (P < 0.001). In all three arms, the reported adverse events were mostly mild. Conclusion After 28 days of follow-up, despite the relatively small sample size used, AL was statistically safe and effective in the treatment of uncomplicated malaria in the NVP-arm. The results of this study also provide an indication of the possible impact of EFV on the performance of AL and the likelihood of it affecting uncomplicated falciparum malaria treatment outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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10. Adherence to antiretroviral therapy among HIV infected children measured by caretaker report, medication return, and drug level in Dar Es Salaam, Tanzania.
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Mghamba, Frida William, Minzi, Omary M. S., Massawe, Augustine, and Sasi, Philip
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ANTIRETROVIRAL agents ,THERAPEUTICS ,HIV infections ,JUVENILE diseases ,NEVIRAPINE ,DRUG administration - Abstract
Background: Adherence to antiretroviral drugs in the treatment of paediatric HIV infection is complicated because of many factors including stigma and drug intake logistics. It is therefore important to identify children with non-adherence in order to intervene before they become at risk of developing treatment failure or drug resistance. The aim of this study was to determine the level of adherence to antiretroviral therapy (ART), measured by caretaker report, medication return and nevirapine plasma concentration. In addition, the association between level of adherence and patient's immune status was compared across the three methods of measuring adherence. Methods: This was a descriptive cross-sectional study involving HIV infected children aged 2-14 years, on nevirapine- based antiretroviral treatment for at least six months, attending care and treatment clinic in three municipal hospitals in Dar- Es- Salaam City. Eligible patients and their accompanying caretakers were consecutively enrolled after obtaining written informed consent. Structured questionnaires were administered to caretakers to assess patient's adherence by caretaker report and medication return whereas a single blood sample for CD4 cell count/percent and determination of nevirapine plasma concentration was taken from patients on the day of assessment. Results: A total of 300 patients and accompanying caretakers were enrolled and the mean patient age (SD) was 8 (3) years. Caretakers' report and medication return showed good adherence (98% and 97%) respectively. However, the level of adherence assessed by nevirapine plasma concentration (85%) was significantly lower than caretaker report and medication return (p < 0.001). The agreement between nevirapine plasma concentration and medication return and between nevirapine plasma concentration and caretaker report was weak (k = 0. 131) (k = 0. 09) respectively. Nevirapine plasma concentration below 3 μg/ml was associated with immunosuppression (p = 0. 021) whereas medication return (>5% of prescribed doses) and caretaker reported missing more than one dose within 72 hours prior to interview were not associated with immunosuppression (p = 0. 474), (p = 0. 569) respectively. Conclusion: Lower adherence level observed using nevirapine plasma concentration and its association with immunological response supports the validity of the method and indicates that adherence data obtained from caretaker report and medication return may overestimate the true adherence in paediatric antiretroviral therapy. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator's product.
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Minzi, Omary M. S., Marealle, Ignace A., Shekalaghe, Seif, Juma, Omar, Ngaimisi, Eliford, Chemba, Mwajuma, Rutaihwa, Mastidia, Abdulla, Salim, and Sasi, Philip
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GENERIC drugs , *MALARIA vaccines , *DRUG tablets , *BIOAVAILABILITY - Abstract
Background: Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa raises a concern on patients achieving therapeutic concentrations after intake of such products. This work compared bioavailability of one generic tablet formulation with innovator's product. Both were fixed dose combination tablet formulations containing artemether and lumefantrine. Methodology: The study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most widely available generic (Artefan®, Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability comparison with Coartem® (Novartis Pharma, Basel, Switzerland) - the innovator's product. A randomized, two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer received Artefan® (test) and Coartem® (as reference) formulation separated by 42 days of drug-free washout period. Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines. Results: The most widely available generic in pharmacies was Artefan® from India. All eighteen enrolled volunteers completed the study and both test and reference tablet formulations were well tolerated. It was possible to quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The geometric mean ratios for Cmax, AUC0-t and AUC0-∞ were 84% in all cases and within FDA recommended bioequivalence limits of 80% -125%, but the 90% confidence intervals were outside FDA recommended limits (CI 49-143%, 53 - 137%, 52 - 135% respectively). There were no statistical significant differences between the two formulations with regard to PK parameters (P > 0.05). Conclusions: Although the ratios of AUCs and Cmax were within the acceptable FDA range, bioequivalence between Artefan® and Coartem® tablet formulations was not demonstrated due to failure to comply with the FDA 90% confidence interval criteria. Based on the observed total drug exposure (AUCs), Artefan® is likely to produce a similar therapeutic response as Coartem®. [ABSTRACT FROM AUTHOR]
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- 2013
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12. Exploration of in vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in under fives in Tabora region, Tanzania.
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Joseph, Deokary, Kabanywanyi, Abdunoor M., Hulser, Ruth, Premji, Zulfiqarali, Minzi, Omary M. S., and Mugittu, Kefas
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DRUG efficacy ,DRUG therapy for malaria ,ANTIMALARIALS ,DRUG dosage ,THERAPEUTICS - Abstract
Background: Tanzania adopted artemether-lumefantrine (AL) as first-line drug for uncomplicated malaria in 2006. Recently, there was an anecdotal report on high malaria recurrence rate following AL treatment in in the (urban and peri-urban), western part of Tanzania. The current report is an exploratory study to carefully and systematically assess AL efficacy in the area. Methods: Between June and August 2011, a total of 1,126 patients were screened for malaria, 33 had malaria, of which 20 patients met inclusion criteria and were enrolled and treated with standard dose of AL as recommended in the WHO protocol. Treated patients were followed up for 28 days to assess treatment responses. Before treatment (Day 0) and post-treatment (Day 7) plasma lumefantrine levels were determined to assess prior AL use and ascertain parasites exposure to adequate plasma leveles of lumefantrine, respectively. Results: The cure rate was 100%. All Day 0 plasma lumefantrine were below HPLC detectable level. The median Day 7 lumefantrine concentration was 404, (range, 189-894 ng/ml). Six out of 20 patients (30%) were gametocytaemic and all cleared gametocytes by Day 14. One patient showed an increase in gametocytes from four on Day 0 to 68, per 500 WBC on Day 2. Conclusion: Artemether lumefantrine is highly efficacious against uncomplicated Plasmodium falciparum malaria. The elevation of gametocytaemia despite AL treatment needs to be evaluated in a larger study. [ABSTRACT FROM AUTHOR]
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- 2013
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13. Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy.
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Mlugu EM, Minzi OMS, Johansson M, Kamuhabwa AAR, and Aklillu E
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- Humans, Female, Pregnancy, Adult, Young Adult, Artemisinins pharmacokinetics, Artemisinins therapeutic use, Artemisinins administration & dosage, Artemisinins blood, Parasitemia blood, Parasitemia prevention & control, Treatment Outcome, Drug Combinations, Adolescent, Piperazines, Quinolines pharmacokinetics, Quinolines blood, Quinolines therapeutic use, Quinolines administration & dosage, Antimalarials pharmacokinetics, Antimalarials therapeutic use, Antimalarials blood, Antimalarials administration & dosage, Pregnancy Complications, Parasitic prevention & control, Pregnancy Complications, Parasitic blood, Malaria prevention & control, Malaria drug therapy
- Abstract
Background: Dihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy., Methods: Malaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively., Results: The incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004)., Conclusion: Lower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP., Trial Registration: Registered 09/12/2016, PACTR201612001901313., (© 2024. The Author(s).)
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- 2024
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14. Efficacy of ivermectin and albendazole combination in suppressing transmission of lymphatic filariasis following mass administration in Tanzania: a prospective cohort study.
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Fimbo AM, Mnkugwe RH, Mlugu EM, Kunambi PP, Malishee A, Minzi OMS, Kamuhabwa AAR, and Aklillu E
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- Tanzania epidemiology, Humans, Prospective Studies, Male, Female, Adult, Middle Aged, Adolescent, Young Adult, Animals, Child, Drug Therapy, Combination, Microfilariae drug effects, Aged, Child, Preschool, Antigens, Helminth blood, Treatment Outcome, Ivermectin therapeutic use, Ivermectin administration & dosage, Albendazole therapeutic use, Albendazole administration & dosage, Elephantiasis, Filarial prevention & control, Elephantiasis, Filarial drug therapy, Elephantiasis, Filarial transmission, Mass Drug Administration, Filaricides therapeutic use, Filaricides administration & dosage
- Abstract
Background: Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA., Methods: This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA., Results: Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA., Conclusions: Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030., (© 2024. The Author(s).)
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- 2024
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15. The effect of sickle cell genotype on the pharmacokinetic properties of artemether-lumefantrine in Tanzanian children.
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Sugiarto SR, Bwire GM, Moore BR, Page-Sharp M, Manning L, Batty KT, Minzi OMS, Ngasala B, Davis TME, Makani J, and Salman S
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- Artemether therapeutic use, Artemether, Lumefantrine Drug Combination therapeutic use, Child, Ethanolamines therapeutic use, Fluorenes therapeutic use, Genotype, Humans, Lumefantrine, Tanzania, Anemia, Sickle Cell drug therapy, Anemia, Sickle Cell genetics, Antimalarials pharmacokinetics, Antimalarials therapeutic use, Malaria drug therapy, Malaria, Falciparum drug therapy
- Abstract
Since there are inconsistent data relating to the effect of haemoglobinopathies on disposition of artemisinin antimalarial combination therapy, and none in sickle cell trait (SCT) or sickle cell disease (SCD), the aim of this study was to characterize the pharmacokinetic properties of artemether-lumefantrine (ARM-LUM) in children with SCD/SCT. Thirty-eight Tanzanian children aged 5-10 years with normal (haemoglobin AA; n = 12), heterozygous (haemoglobin AS; n = 14) or homozygous (haemoglobin SS; n = 12) sickle genotypes received six ARM-LUM doses (1.7 mg/kg plus 10 mg/kg, respectively) over 3 days. Sparse venous and mixed-capillary dried blood spot (DBS) samples were taken over 42 days. Plasma and DBS ARM and LUM, and their active metabolites dihydroartemisinin (DHA) and desbutyl-lumefantrine (DBL), were assayed using validated liquid chromatography-mass spectrometry. Multi-compartmental pharmacokinetic models were developed using a population approach. Plasma but not DBS concentrations of ARM/DHA were assessable. The majority (85%) of the 15 measurable values were within 95% prediction intervals from a published population pharmacokinetic ARM/DHA model in Papua New Guinean children of similar age without SCD/SCT who had uncomplicated malaria, and there was no clear sickle genotype clustering. Plasma (n = 38) and corrected DBS (n = 222) LUM concentrations were analysed using a two-compartment model. The median [inter-quartile range] LUM AUC
0-∞ was 607,296 [426,480-860,773] μg.h/L, within the range in published studies involving different populations, age-groups and malaria status. DBS and plasma DBL concentrations correlated poorly and were not modelled. These data support use of the conventional ARM-LUM treatment regimen for uncomplicated malaria in children with SCT/SCD., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2022
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16. Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania.
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Fimbo AM, Minzi OMS, Mmbando BP, Barry A, Nkayamba AF, Mwamwitwa KW, Malishee A, Seth MD, Makunde WH, Gurumurthy P, Lusingu JPA, Kamuhabwa AAR, and Aklillu E
- Abstract
Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1-6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age ( p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA ( p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.
- Published
- 2020
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17. Pregnancy and CYP3A5 Genotype Affect Day 7 Plasma Lumefantrine Concentrations.
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Mutagonda RF, Minzi OMS, Massawe SN, Asghar M, Färnert A, Kamuhabwa AAR, and Aklillu E
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- Antimalarials therapeutic use, Artemether, Lumefantrine Drug Combination therapeutic use, Cohort Studies, Dose-Response Relationship, Drug, Female, Gene Frequency, Genotype, Humans, Malaria, Falciparum blood, Malaria, Falciparum genetics, Pregnancy, Pregnancy Complications, Parasitic blood, Pregnancy Complications, Parasitic genetics, Pregnancy Trimester, Third, Prospective Studies, Time Factors, Antimalarials administration & dosage, Antimalarials blood, Artemether, Lumefantrine Drug Combination administration & dosage, Artemether, Lumefantrine Drug Combination blood, Cytochrome P-450 CYP3A genetics, Malaria, Falciparum drug therapy, Pregnancy Complications, Parasitic drug therapy
- Abstract
Pregnancy and pharmacogenetics variation alter drug disposition and treatment outcome. The objective of this study was to investigate the effect of pregnancy and pharmacogenetics variation on day 7 lumefantrine (LF) plasma concentration and therapeutic responses in malaria-infected women treated with artemether-lumefantrine (ALu) in Tanzania. A total of 277 (205 pregnant and 72 nonpregnant) women with uncomplicated Plasmodium falciparum malaria were enrolled. Patients were treated with ALu and followed up for 28 days. CYP3A4 , CYP3A5 , and ABCB1 genotyping were done. Day 7 plasma LF concentration and the polymerase chain reaction (PCR) - corrected adequate clinical and parasitological response (ACPR) at day 28 were determined. The mean day 7 plasma LF concentrations were significantly lower in pregnant women than nonpregnant women [geometric mean ratio = 1.40; 95% confidence interval (CI) of geometric mean ratio (1.119-1.1745), P < 0.003]. Pregnancy, low body weight, and CYP3A5*1/*1 genotype were significantly associated with low day 7 LF plasma concentration ( P < 0.01). PCR-corrected ACPR was 93% (95% CI = 89.4-96.6) in pregnant women and 95.7% (95% CI = 90.7-100) in nonpregnant women. Patients with lower day 7 LF concentration had a high risk of treatment failure (mean 652 vs. 232 ng/ml, P < 0.001). In conclusion, pregnancy, low body weight, and CYP3A5*1 allele are significant predictors of low day 7 LF plasma exposure. In turn, lower day 7 LF concentration is associated with a higher risk of recrudescence. SIGNIFICANCE STATEMENT: This study reports a number of factors contributing to the lower day 7 lumefantrine (LF) concentration in women, which includes pregnancy, body weight, and CYP3A5*1/*1 genotype. It also shows that day 7 LF concentration is a main predictor of malaria treatment. These findings highlight the need to look into artemether-LF dosage adjustment in pregnant women so as to be able to maintain adequate drug concentration, which is required to reduce treatment failure rates in pregnant women., Competing Interests: This work was supported by grants from the Swedish International Development Cooperation Agency Programme under Muhimbili University of Health and Allied Sciences Reproductive health projects. The authors declare that they have no competing interests., (Copyright © 2019 The Author(s).)
- Published
- 2019
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18. Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population: a concern about the metabolism of artemisinin-based combinations.
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Marwa KJ, Schmidt T, Sjögren M, Minzi OM, Kamugisha E, and Swedberg G
- Subjects
- Adult, Antimalarials therapeutic use, Artemisinins therapeutic use, Cross-Sectional Studies, Female, Gene Frequency, Humans, Malaria drug therapy, Malaria epidemiology, Male, Polymorphism, Restriction Fragment Length, Tanzania epidemiology, Young Adult, Antimalarials pharmacokinetics, Artemisinins pharmacokinetics, Cytochrome P-450 Enzyme System genetics, Malaria genetics, Polymorphism, Single Nucleotide genetics
- 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™ 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.
- Published
- 2014
- Full Text
- View/download PDF
19. Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania.
- Author
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Mugusi SF, Ngaimisi E, Janabi MY, Mugusi FM, Minzi OM, Sasi PG, Bakari M, Lindquist L, Aklillu E, and Sandstrom EG
- Subjects
- AIDS-Related Opportunistic Infections mortality, Adult, Alkynes, Antiretroviral Therapy, Highly Active, Benzoxazines therapeutic use, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Candidiasis, Oral complications, Candidiasis, Oral mortality, Cohort Studies, Coinfection, Cyclopropanes, Female, HIV Infections complications, HIV Infections pathology, Humans, Karnofsky Performance Status, Leukocyte Count, Male, Middle Aged, Risk Factors, Sarcoma, Kaposi complications, Sarcoma, Kaposi mortality, Tanzania, Tuberculosis complications, Tuberculosis pathology, HIV Infections mortality, Tuberculosis mortality
- Abstract
Background: The aim of this study was to describe risk factors for mortality and clinical characteristics of HIV-infected patients with and without tuberculosis (TB) coinfection., Methods: A cohort of HIV-infected patients with CD4(+) T-cell counts of ≤200 cells/μl was recruited, consisting of 255 HIV-infected patients without active TB and 231 patients with active TB. All received a well-supervised treatment with an efavirenz-based HAART, and those coinfected with TB received appropriate anti-TB treatment. They were followed up for 48 weeks after HAART initiation., Results: Common presenting symptoms in HIV-only patients were fever (36.5%), headache (34.5%), skin rash (34.5%) and weight loss (32%), while in HIV-TB patients the symptoms were weight loss (58%), cough (57.6%), night sweats (44.6%) and fever (34.2%). HIV-TB patients had significantly lower body mass index, Karnofsky scores and haemoglobin levels compared to those infected with HIV only, despite similar baseline CD4(+) T-cell counts. Overall, 12 (4.7%) HIV patients developed TB and 7 (3%) HIV-TB patients had worsening of their TB symptoms during the study period. Mortality was similar in the two groups, being 10.9% (16 deaths per 100 person years) and 11.3% (17 deaths per 100 person years) in HIV-only and HIV-TB patients, respectively. Overall, more males (13.1%) died compared to females (9.6%). Predictors of mortality were presence of oral candidiasis, Kaposi's sarcoma, low Karnofsky score, and low baseline white blood cell and CD4(+) T-cell counts., Conclusions: The outcomes following well-supervised treatment of HIV-TB patients are similar to those in patients with HIV alone. Predictors of mortality were those of advanced disease.
- Published
- 2012
- Full Text
- View/download PDF
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