Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments

Sowunmi, A.; Akano, Kazeem; Ntadom, Godwin; Ayede, Adejumoke Idowu; Ibironke, Folasade O.; Aderoyeje, Temitope; Adewoye, Elsie O.; Fatunmbi, Bayo; Oguche, Stephen; Okafor, Henrietta U.; Watila, Ismaila; Meremikwu, Martin; Agomo, Philip; Ogala, WN; Agomo, Chimere; Folarin, Onikepe A.; Gbotosho, Grace O.; Happi, Christian T.

doi:10.1186/s40249-016-0217-7

Cited by 15 publications

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“…However, the prevalence of anaemia at presentation and the burden of anaemia following a single episode of infection appeared to have been little affected. The low gametocyte carriage ten years following adoption as first-line antimalarials can be attributable to rapid clearance of asexual parasitaemia [ 17 , 23 , 30 , 31 ] and alteration in gametocyte sex ratios [ 32 , 33 ] which can produce a female bias sex ratio that is less infective to mosquitoes [ 34 ]. It has also been postulated that ACTs can mobilize immature gametocytes from bone marrow to peripheral blood where they can be rapidly eliminated by components of ACTs [ 30 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

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Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials

et al. 2017

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BackgroundArtemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children.MethodsMalarious <5 year-olds randomized to artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine treatments were followed up clinically for 6 weeks. Anaemia was defined as haematocrit <30%; Malaria-attributable fall in haematocrit (MAFH) as the difference between haematocrit 28–42 days post- and pre-treatment; Total MAFH (TMAFH) as the difference between days 28–42 haematocrit and the lowest haematocrit recorded in the first week post-treatment initiation; Drug-attributable fall in haematocrit (DAFH) as the difference between MAFH and TMAFH; Early appearing anaemia (EAA) as haematocrit <30% occurring within 1 week in children with normal haematocrit pre-treatment. Predictors of anaemia pre-treatment, EAA, MAFH or DAFH >4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively.ResultsPre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL−1 were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL−1, parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL−1. In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9–2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children.ConclusionAfter ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children.Trial registrationPan African Clinical Trial Registry (PACTR) [PACTR201709002064150, 1 March 2017].

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Section: Discussionmentioning

confidence: 99%

“…5 ). This finding in anaemic children suggests considerable degree of “haematocrit conservation” [ 31 , 35 ]. Taking together, this would suggest the three ACTs may prevent further falls in haematocrit in anaemic children at presentation and in half of non-anaemic children at presentation.…”

Section: Discussionmentioning

confidence: 99%

Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials

et al. 2017

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“…These include the less frequent use of DHP compared to AL as evidenced, for example, by the non-inclusion of DHP in the National Guidelines as one of the recommended ACTs in Nigeria [ 18 ], and distribution data showing lesser utilisation of AA (approximately 10–25%) both in private and public sectors in the six states of Nigeria targeted for ACT coverage under The Global Fund and World Bank Project. In addition, after seven years of adoption, AA is more efficacious than AL in acutely malarious Nigerian children [ 8 , 13 ]. It is also likely that the less frequent use of DHP and AA, and the little or no use of chloroquine following adoption of ACTs as first-line antimalarials, partly contributed to the superior efficacy of artemisinin-4-aminoquinoline combinations over AL [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Asexual parasite positivity on day 3 (APPD3) was defined as the proportion of children with residual asexual parasitaemia three days after treatment initiation. Parasite clearance time (PCT) was defined as the time elapsing between drug administration and absence of microscopic detection of peripheral asexual parasitaemia [ 3 , 13 ].…”

Section: Methodsmentioning

confidence: 99%

Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children

et al. 2018

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BackgroundIn acute falciparum malaria, asexual parasite reduction ratio two days post-treatment initiation (PRRD2) ≥ 10 000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives. However, there is little evaluation of alternative measures; for example, parasite reduction ratio one day after treatment initiation (PRRD1) and its relationship with parasite clearance time (PCT) or PRRD2. This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs.MethodsIn acutely malarious children treated with artesunate-amodiaquine (AA), artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHP), the relationships between PRRD1 or PRRD2 and PCT, and between PRRD1 and PRRD2 were evaluated using linear regression. Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis. Predictors of PRRD1 > 5000 per half cycle and PRRD2 ≥ 10 000 per cycle were evaluated using stepwise multiple logistic regression models. Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase, PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half.ResultsIn 919 malarious children, PRRD1 was significantly higher in DHP- and AA-treated compared with AL-treated children (P < 0.0001). PRRD1 or PRRD2 values correlated significantly negatively with PCT values (P < 0.0001 for each) and significantly positively with each other (P < 0.0001). PCT estimates from linear regression equations for PRRD1 and PRRD2 showed insignificant bias on the Bland-Altman plot (P = 0.7) indicating the estimates can be used interchangeably. At presentation, age > 15 months, parasitaemia > 10 000/μl and DHP treatment independently predicted PRRD1 > 5000 per half cycle, while age > 30 months, haematocrit ≥31%, body temperature > 37.4 °C, parasitaemia > 100 000/μl, PRRD1 value > 1000 and no gametocytaemia independently predicted PRRD2 ≥ 10 000 per cycle. Using the linear regression equation generated during the early phase in 166 DHP-treated children, PCT estimates and PCTs determined by microscopy in the 155 children in the later phase were similar in the same patients.ConclusionsPRRD1 and estimates of PCT using PRRD1 linear regression equation of PRRD1 and PCT can be used in therapeutic efficacy studies.Trial registrationPan African Clinical Trial Registration PACTR201709002064150, 1 March 2017, http://www.pactr.org

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“…However, P. falciparum has been recently reported to be resistant to artemisinin in Greater Mekong Subregion [11,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

Teklemichael

Mizukami

Toume

et al. 2020

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Background: The herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, examined a variety of Japanese traditional herbal medicine (Kampo) for their potential antimalarial activities. Methods: We designed a comprehensive screening to identify novel antimalarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n=96). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and -resistant (Dd2) strains of Plasmodium falciparum . The cytotoxicity was also evaluated using primary Adult Mouse Brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo antimalarial activity. Results: Out of 120 herbal extracts, Coptis Rhizome showed the highest antimalarial activity (IC 50 1.9 µg/mL of 3D7 and 4.85 µg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis Rhizome also showed antimalarial activities with IC 50 1.1, 2.6, and 6.0 µM (against 3D7) and 3.1, 6.3, and 11.8 µM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest antimalarial activity (IC 50 1.1 µM against 3D7 and 3.1 µM against Dd2) with SI of 37.8 and 13.2, respectively. . Finally, the herbal extract of Coptis Rhizome and its major active compound coptisine chloride exhibited significant antimalarial activity in mice infected with P. yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P <.05) for Coptis Rhizome and from 81 to 89% (P <.01) for coptisine chloride. Conclusion: Coptis Rhizome and its major active compound coptisine chloride showed promising antimalarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus Kampo herbal medicine is a potential natural resource for novel antipathogenic agents.

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Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments

Cited by 15 publications

References 47 publications

Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials

Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials

Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

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