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

Mnkugwe, Rajabu Hussein; Minzi, Omary; Kinung’hi, Safari; Kamuhabwa, Appolinary; Aklillu, Eleni

doi:10.1371/journal.pntd.0008619

Cited by 30 publications

(29 citation statements)

References 39 publications

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“…Repeated doses of PZQ or combining it with other anthelmintics that kills the juvenile schistosome is recommended to improve the efficacy against schistosomiasis (Munisi et al, 2017;Bergquist and Elmorshedy, 2018). A recent randomized clinical trial reported superior efficacy of PZQ and Dihydroartemisininpiperaquine combination therapy (targeting both the adult and juvenile worm, respectively) than PZQ alone for treating intestinal schistosomiasis (Mnkugwe et al, 2020a). The cure rate significantly varied across the infection intensity groups at baseline.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the reported low cure rate and reduced efficacy of PZQ after repeated administration in some areas, the WHO recommends that the NTD programs implementing MDA of PZQ to incorporate regular efficacy assessment in their working standard to monitor and evaluate the efficacy of the drug (WHO, 2010(WHO, , 2015a. To sustain the impact of preventive chemotherapy and avoid possible future parasite resistance, additional measures like availing adequate clean water, implementing hygiene and sanitation programs, educating the community, and exploring other treatment options are crucial (Mnkugwe et al, 2020a).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of praziquantel preventive chemotherapy in Schistosoma mansoni infected school children in Southern Ethiopia: A prospective cohort study

Gebreyesus

Makonnen²,

Tadele³

et al. 2023

Front. Pharmacol.

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Background: The World Health Organization recommends efficacy and safety surveillance of anti-helminths used in mass drug administration campaigns. We evaluated the effectiveness of single-dose praziquantel against Schistosoma mansoni infection, and the safety of praziquantel plus albendazole preventive chemotherapy (PC) in Schistosoma mansoni infected school children (n = 512) in Southern Ethiopia.Method: Stool examinations were done using thick smear Kato-Katz at baseline, week-4, and week-8 of post-Mass drug administration (MDA) to assess praziquantel efficacy. Participants were followed for MDA-associated adverse events up to day 7 of post-MDA. The primary and secondary study outcomes were praziquantel efficacy (parasitological cure and egg reduction rates) and MDA-associated adverse events (AEs), respectively.Result: The overall cure rates at week-4 and week-8 were 89.1% (95%CI = 86.1–91.7) and 87.5% (95%CI = 83.6–90.8), respectively. Cure rates among moderate-to-heavily infected children were significantly lower (p = 0.001) compared to those with light infection at week-4 (84.4% vs. 91.1%, p = 0.03) and week-8 (78.6% vs. 91.9%, respectively). Older children had a higher cure rate than younger ones at week-8 (90.1% vs. 79.5%, p = 0.01). Among those who were Schistosoma egg-free (cured) at week 4, 7.8% became egg-positive at week 8. The overall egg reduction rate (ERR) at week-4 and week-8 were 93.5% and 91.3%, respectively, being lower among the 5–9 years old age groups (p = 0.01) at week-8. The proportion of children who remained schistosoma egg-positive throughout the study follow-up period was 4.6%, and their ERR at week-4 and week-8 was 50% and 51%, respectively, which is below the 90% World Health Organization threshold for efficacy. The incidence of experiencing at least one type of MDA-associated AEs were 17.0% (95%CI = 13.8%–20.5%); abdominal pain, headache, and vomiting were the most common. The proportion of mild, moderate, and severe AEs was 63.2%, 26.3%, and 10.5%, respectively. Females experienced more AEs than males (p = 0.03).Conclusion: Single-dose praziquantel is still effective for the treatment of intestinal schistosomiasis. Praziquantel and albendazole preventive chemotherapy is safe and tolerable, and associated AEs are mostly mild-to-moderate and transient. However, the reduced PZQ effectiveness in moderate-to-heavy infection and observed AEs in about one-fifth of infected children underscores the need for better treatment strategies and surveillance for early detection of parasite resistance and management of AEs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of praziquantel preventive chemotherapy in Schistosoma mansoni infected school children in Southern Ethiopia: A prospective cohort study

Gebreyesus

Makonnen²,

Tadele³

et al. 2023

Front. Pharmacol.

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“…School deworming programmes are practiced yearly in Tanzania [ 20 , 21 , 80 ], but it seems there are still some pockets especially in hard to reach areas such as Kwakibuyu village where coverage could be sub optimal (55% of children reported to have received deworming drugs including those for schistosomiasis in the past 6 months). It is also possible that drugs such as Praziquantel used for treatment and control of schistosomiasis wanes too early that only a single round per year would not be sufficient for protection in the entire period [ 81 ], especially in areas with high transmission like Kwakibuyu.…”

Section: Discussionmentioning

confidence: 99%

Attributable risk factors for asymptomatic malaria and anaemia and their association with cognitive and psychomotor functions in schoolchildren of north-eastern Tanzania

et al. 2022

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In Africa, children aged 5 to 15 years (school age) comprises more than 50% (>339 million) of the under 19 years population, and are highly burdened by malaria and anaemia that impair cognitive development. For the prospects of improving health in African citizens, understanding malaria and its relation to anaemia in school-aged children, it is crucial to inform targeted interventions for malaria control and accelerate elimination efforts as part of improved school health policy. We conducted a study to determine the risk factors for asymptomatic malaria and their association to anaemia. We explored the prevalence of antimalarial drug resistance as well as the association of asymptomatic malaria infection and anaemia on cognitive and psychomotor functions in school-aged children living in high endemic areas. This study was a comprehensive baseline survey, within the scope of a randomised, controlled trial on the effectiveness and safety of antimalarial drugs in preventing malaria and its related morbidity in schoolchildren. We enrolled 1,587 schoolchildren from 7 primary schools located in Muheza, north-eastern Tanzania. Finger-pricked blood samples were collected for estimation of malaria parasitaemia using a microscope, haemoglobin concentration using a haemoglobinometer, and markers of drug resistance processed from dried blood spots (DBS). Psychomotor and Cognitive functions were assessed using a ‘20 metre Shuttle run’ and a test of everyday attention for children (TEA-Ch), respectively. The prevalence of asymptomatic malaria parasitaemia, anaemia and stunting was 26.4%, 49.8%, and 21.0%, respectively with marked variation across schools. In multivariate models, asymptomatic malaria parasitaemia attributed to 61% of anaemia with a respective population attribution fraction of 16%. Stunting, not sleeping under a bednet and illiterate parent or guardian were other factors attributing to 7%, 9%, and 5% of anaemia in the study population, respectively. Factors such as age group (10–15 years), not sleeping under a bednet, low socioeconomic status, parents’ or guardians’ with a low level of education, children overcrowding in a household, and fewer rooms in a household were significantly attributed to higher malaria infection. There was no significant association between malaria infection or anaemia and performance on tests of cognitive function (sustained attention) or psychomotor function (VO2 max). However, a history of malaria in the past one month was significantly associated with decreased cognitive scores (aOR = -4.1, 95% CI -7.7–0.6, p = 0.02). Furthermore, stunted children had significantly lower VO2max scores (aOR = -1.9, 95% CI -3.0–0.8, p = 0.001). Regarding the antimalarial drug resistance markers, the most prevalent Pfmdr1 86-184-1034-1042-1246 haplotypes were the NFSND in 47% (n = 88) and the NYSND in 52% (n = 98). The wild type Pfcrt haplotypes (codons 72–76, CVMNK) were found in 99.1% (n = 219) of the samples. Malaria, stunting and parents’ or guardians’ illiteracy were the key attributable factors for anaemia in schoolchildren. Given malaria infection in schoolchildren is mostly asymptomatic; an addition of interventional programmes such as intermittent preventive treatment of malaria in schoolchildren (IPTsc) would probably act as a potential solution while calling for an improvement in the current tools such as bednet use, school food programme, and community-based (customised) health education with an emphasis on nutrition and malaria control.

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“…Evidence has shown that intestinal schistosomiasis is associated with adverse birth outcomes [18,19]. DP has been found to be effective against intestinal schistosomiasis [20]. This may partly explain the observed nonmalaria effect of DP, although the exact non-malarial mechanisms by which DP is improving birth weight are still not clear and warrant further study.…”

Section: Discussionmentioning

confidence: 99%

Superiority trial of intermittent treatment with dihydroartemisinin–piperaquine versus sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy

et al. 2023

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Background Malaria in pregnancy is responsible for various adverse maternal and birth outcomes. The emerging resistance to sulfadoxine–pyrimethamine (SP) raises important concerns about its use for intermittent preventive treatment in pregnancy (IPTp) in Africa. This trial aimed to assess the efficacy and safety of IPTp with dihydroartemisinin–piperaquine (DP) as an alternative to IPTp with SP. Results The double-blind, randomized, and controlled superiority trial was conducted between July 2020 and June 2021. A total of 250 women were enrolled and randomly assigned to receive SP (n = 125) or DP (n = 125). Two hundred and six (82.4%) participants that contributed to the outcomes were included in the modified intention-to-treat (ITT) analysis, while 84 participants that completed the three courses of the study drugs were included in the per protocol (PP) analysis. The ITT analysis results showed that the incidence of histopathologically confirmed placental malaria was nonsignificantly higher in the DP group compared with the SP group (62.5% vs. 51.1%, P = 0.098). After adjusting for confounders, the risk of histopathologically confirmed placental malaria was also nonsignificantly higher in the DP group (Adjusted Relative Risk [RR] = 1.27, 95% CI 0.94–1.71) compared with the SP group. In contrast, the risk of a low APGAR score was significantly lower in the DP group (RR = 0.45, 95% CI 0.38–0.52) compared with the SP group. Also, the risk of a composite adverse birth outcome (low birth weight or preterm delivery or neonates small for the gestational age) was nonsignificantly lower in the DP group (Adjusted RR = 0.82, 95% CI 0.55–1.21) compared with the SP group. Both drugs were well tolerated, although nausea and vomiting occurred in a significant number of participants in the SP group. Conclusions A three-course IPTp with DP was safe and was not found to be superior to IPTp with SP in the prevention of placental malaria. Although IPTp with DP was associated with a significant lower risk of low APGAR score and nonsignificant lower risks of other adverse birth outcomes compared with IPTp with SP. Trial registration PACTR, PACTR202002644579177. Registered 20 February 2020, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9753.

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

Cited by 30 publications

References 39 publications

Efficacy and safety of praziquantel preventive chemotherapy in Schistosoma mansoni infected school children in Southern Ethiopia: A prospective cohort study

Efficacy and safety of praziquantel preventive chemotherapy in Schistosoma mansoni infected school children in Southern Ethiopia: A prospective cohort study

Attributable risk factors for asymptomatic malaria and anaemia and their association with cognitive and psychomotor functions in schoolchildren of north-eastern Tanzania

Superiority trial of intermittent treatment with dihydroartemisinin–piperaquine versus sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy

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