Participatory integrated control strategies and elimination of schistosomiasis in sub-Saharan Africa

Mazigo, Humphrey D.

doi:10.1016/s2214-109x(19)30271-2

Cited by 18 publications

(17 citation statements)

References 6 publications

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“…PZQ is reported to be safe and efficacious against all Schistosoma species, including Schistosoma haematobium (urogenital schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis). Globally, more than 800 million people are at risk of schistosomiasis infection, and about 250 million are infected and need treatment ( Hotez et al, 2014 ; Mazigo, 2019 ). In Tanzania, schistosomiasis was first reported back in 1895 ( Doumenge et al, 1984 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania

et al. 2021

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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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Section: Introductionmentioning

confidence: 99%

Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania

et al. 2021

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“…Schistosomiasis is a poverty-related parasitic infection that prevails in rural and disadvantaged populations in the tropics and sub-tropics regions [ 1 , 2 ]. It is estimated that more than 250 million people are infected with schistosomiasis globally [ 3 , 4 ]. A large proportion of the global burden is from children of Sub-Saharan Africa (SSA) [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection

et al. 2021

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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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“…Schistosomiasis is among the Neglected Tropical Diseases (NTDs) that continue to be of major public health importance, especially among school-going children in Sub Saharan Africa (SSA) [ 1 ]. This region harbors more than 90% of the 250 million cases reported globally [ 2 , 3 ], and more than 280,000 deaths annually [ 2 , 4 ]. Among parasitic diseases, schistosomiasis is second only to malaria in terms of morbidity and mortality, particularly among children [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of praziquantel and dihydroartemisinin piperaquine combination for treatment and control of intestinal schistosomiasis: A randomized, non-inferiority clinical trial

et al. 2020

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Participatory integrated control strategies and elimination of schistosomiasis in sub-Saharan Africa

Cited by 18 publications

References 6 publications

Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania

Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania

Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection

Efficacy and safety of praziquantel and dihydroartemisinin piperaquine combination for treatment and control of intestinal schistosomiasis: A randomized, non-inferiority clinical trial

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