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- Barry, A, et al.
(författare)
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Comparative Assessment of the Pharmacovigilance Systems within the Neglected Tropical Diseases Programs in East Africa-Ethiopia, Kenya, Rwanda, and Tanzania
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring the safety of medicines used in public health programs (PHPs), including the neglected tropical diseases (NTD) program, is a WHO recommendation, and requires a well-established and robust pharmacovigilance system. The objective of this study was to assess the pharmacovigilance systems within the NTD programs in Ethiopia, Kenya, Rwanda, and Tanzania. The East African Community Harmonized Pharmacovigilance Indicators tool for PHPs was used to interview the staff of the national NTD programs. Data on four components, (i) systems, structures, and stakeholder coordination; (ii) data management and signal generation; (iii) risk assessment and evaluation; and (iv) risk management and communication, were collected and analyzed. The NTD programs in the four countries had a strategic master plan, with pharmacovigilance components and mechanisms to disseminate pharmacovigilance information. However, zero individual case safety reports were received in the last 12 months (2017/2018). There was either limited or no collaboration between the NTD programs and their respective national pharmacovigilance centers. None of the NTD programs had a specific budget for pharmacovigilance. The NTD program in all four countries had some safety monitoring elements. However, key elements, such as the reporting of adverse events, collaboration with national pharmacovigilance centers, and budget for pharmacovigilance activity, were limited/missing.
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| 3. |
- Minzi, OM, et al.
(författare)
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Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection
- 2021
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Ingår i: Pharmaceuticals (Basel, Switzerland). - : MDPI AG. - 1424-8247. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Praziquantel (PZQ) and dihydroartemisinin-piperaquine (DHP) combination recently showed superior effectiveness than PZQ alone to treat intestinal schistosomiasis. In this follow-up study, we investigated the effect of DHP co-administration on the pharmacokinetics of PZQ and its enantiomers among 64 Schistosoma mansoni infected children treated with PZQ alone (n = 32) or PZQ + DHP combination (n = 32). Plasma samples collected at 0, 1, 2, 4, 6, and 8 h post-dose were quantified using UPLCMS/MS. The geometric mean (GM) of AUCs for total PZQ, R-PZQ and S-PZQ were significantly higher among children who received PZQ + DHP than PZQ alone. The geometric mean ratio (GMR) and (90% CI) of AUC0–∞ for PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 2.18 (1.27, 3.76), 3.98 (2.27, 7.0) and 1.86 (1.06, 3.28), respectively. The GMR and (90% CI) of AUC0–8 for total PZQ, R-PZQ, and S-PZQ were 1.73 (1.12, 2.69), 2.94 (1.75, 4.92), and 1.50 (0.97, 2.31), respectively. The GM of Cmax for total PZQ, R-PZQ and S-PZQ were significantly higher among those who received PZQ + DHP than PZQ alone. The GMR (90% CI) of Cmax of PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 1.75 (1.15, 2.65), 3.08 (1.91, 4.96), and 1.50 (1.0, 2.25%), respectively. The 90% CI of the GMRs for both AUCs and Cmax for total PZQ, R-PZQ, and S-PZQ were outside the acceptable 0.80–1.25 range, indicating that the two treatment arms were not bioequivalent. DHP co-administration significantly increases systemic PZQ exposure, and this may contribute to increased effectiveness of PZQ + DHP combination therapy than PZQ alone to treat schistosomiasis.
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| 4. |
- Fimbo, AM, et al.
(författare)
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Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:5
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Tidskriftsartikel (refereegranskat)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.
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| 9. |
- Mlugu, EM, et al.
(författare)
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Effectiveness of Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment of Malaria and Adverse Birth Outcomes in Pregnant Women
- 2020
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine–pyrimethamine (IPTp-SP) for prevention of malaria and adverse birth outcomes can be compromised by parasites-resistance to sulfadoxine–pyrimethamine. This study prospectively evaluated the effectiveness of IPTp-SP in Southeast Tanzania. From January 2017 to May 2019, HIV-negative and malaria-negative (mRDT) pregnant women attending their first antenatal-care visit in the second or third trimester (n = 500) were enrolled to receive monthly IPTp-SP and followed the protocol till delivery. The primary outcome was the prevalence of histopathological placental malaria. Secondary outcomes were anemia, malaria parasites detected during pregnancy and at delivery, adverse birth outcomes (low-birth-weight [LBW], premature birth, fetal anemia, still birth, and spontaneous abortion). Rates of histopathological placental malaria, any parasitemia at delivery (placental, cord or maternal), and any adverse birth outcome were 9.4%, 20.9%, and 26.5%, respectively. Rates of symptomatic malaria and parasitemia during pregnancy were 2.8% and 16%, respectively. Histopathological placental malaria significantly increased the odds of any adverse birth outcomes, particularly LBW. IPTp-SP with more than or equal to three doses significantly improved birth weight and reduced the risk of LBW by 56% compared to <3 SP doses (p = 0.009). IPTp-SP with more than or equal to three doses is still effective in improving birth weight. However, the detection of histopathological placental-malaria in one-tenth and parasitemia in one-fifth of pregnant women reflects the need to optimize the prevention of malaria during pregnancy.
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| 10. |
- Mnkugwe, RH, et al.
(författare)
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Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania
- 2021
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Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12, s. 712084-
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Tidskriftsartikel (refereegranskat)abstract
- Studies on pharmacogenetics of praziquantel (PZQ) and its relevance on plasma drug concentrations and schistosomiasis treatment outcomes are lacking. We investigated the effect of pharmacogenetics variations of PZQ on plasma drug levels and schistosomiasis treatment outcomes among infected Tanzanian school-aged children. A total of 340 Schistosoma mansoni infected children were enrolled and treated with single-dose PZQ. Stool samples analysis was done by thick smear Kato-Katz technique, and treatment efficacy was assessed at 3-weeks post-treatment. Safety was assessed within 4 h after PZQ intake. Plasma samples were collected at 4 h post-dose, and PZQ and trans-4-OH-PZQ concentrations were quantified using UPLCMS/MS. Genotyping for CYP3A4*1B, CYP3A5 (*3, *6, *7), CYP2C19 (*2, *3, *17), and CYP2C9 (*2, *3) were done by Real-Time PCR. The median age (range) of the study participants was 12 years (7–17). There was a significant association of CYP2C19 genotypes with PZQ concentrations and its metabolic ratio (trans-4-OH-PZQ/PZQ). PZQ concentration was significantly higher among CYP2C19 (*2, *3) carriers than CYP2C19 *1/*1 and CYP2C19 *17 carriers (ultra-rapid metabolizers) (p = 0.04). The metabolic ratio was significantly higher among CYP2C19*17 carriers than CYP2C19 (*2, *3) carriers (p = 0.01). No significant effect of CYP3A4, CYP3A5, CYP2C19, and CYP2C9 genotypes on treatment efficacy or adverse events were observed. Baseline infection intensity and CYP3A5 genotype were significant predictors of treatment associated-adverse events. In conclusion, CYP2C19 genotype significantly affects plasma PZQ concentration and its metabolic ratio. For the first time, we report the importance of pharmacogenetic variation for the treatment of schistosomiasis, a neglected tropical disease.
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