Pharmacokinetic considerations in seasonal malaria chemoprevention

Chotsiri, Palang; White, Nicholas J.; Tärning, Joel

doi:10.1016/j.pt.2022.05.003

Cited by 14 publications

(16 citation statements)

References 41 publications

(51 reference statements)

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“…Interestingly, we show that the effect of SMC is particularly pronounced in the dry season rather than the rainy season. We hypothesise that SMC results in CU5 either being fully protected from infection or, if infected, only having infections with low parasitaemia (which may be due to incomplete adherence to the 3-day regimen or drug resistance) 38. Combined with the lower abundance and density of mosquitoes during the dry season, this then results in lower transmission rates, which leads to a lower incidence.…”

Section: Discussionmentioning

confidence: 99%

Malaria trends in districts that were targeted and not-targeted for seasonal malaria chemoprevention in children under 5 years of age in Guinea, 2014–2021

Bisanzio,

Keita,

Camara

et al. 2024

BMJ Glob Health

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BackgroundSeasonal malaria chemoprevention (SMC) is a main intervention to prevent and reduce childhood malaria. Since 2015, Guinea has implemented SMC targeting children aged 3–59 months (CU5) in districts with high and seasonal malaria transmission.ObjectiveWe assessed the programmatic impact of SMC in Guinea’s context of scaled up malaria intervention programming by comparing malaria-related outcomes in 14 districts that had or had not been targeted for SMC.MethodsUsing routine health management information system data, we compared the district-level monthly test positivity rate (TPR) and monthly uncomplicated and severe malaria incidence for the whole population and disaggregated age groups (<5 years and ≥5 years of age). Changes in malaria indicators through time were analysed by calculating the district-level compound annual growth rate (CAGR) from 2014 to 2021; we used statistical analyses to describe trends in tested clinical cases, TPR, uncomplicated malaria incidence and severe malaria incidence.ResultsThe CAGR of TPR of all age groups was statistically lower in SMC (median=−7.8%) compared with non-SMC (median=−3.0%) districts. Similarly, the CAGR in uncomplicated malaria incidence was significantly lower in SMC (median=1.8%) compared with non-SMC (median=11.5%) districts. For both TPR and uncomplicated malaria incidence, the observed difference was also significant when age disaggregated. The CAGR of severe malaria incidence showed that all age groups experienced a decline in severe malaria in both SMC and non-SMC districts. However, this decline was significantly higher in SMC (median=−22.3%) than in non-SMC (median=−5.1%) districts for the entire population, as well as both CU5 and people over 5 years of age.ConclusionEven in an operational programming context, adding SMC to the malaria intervention package yields a positive epidemiological impact and results in a greater reduction in TPR, as well as the incidence of uncomplicated and severe malaria in CU5.

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Section: Discussionmentioning

confidence: 99%

Malaria trends in districts that were targeted and not-targeted for seasonal malaria chemoprevention in children under 5 years of age in Guinea, 2014–2021

Bisanzio,

Keita,

Camara

et al. 2024

BMJ Glob Health

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“…In Africa, artemether-LMF accounts for 75% of the antimalarial drug market ( 1 ). Recent studies have shown excellent efficacy of DHA-PPQ either for intermittent preventive treatment of infants or pregnant women or for seasonal malaria chemoprevention ( 74 ). Our data lend support to the introduction of DHA-PPQ into areas with artemether-LMF use.…”

Section: Discussionmentioning

confidence: 99%

Mapping the genomic landscape of multidrug resistance in Plasmodium falciparum and its impact on parasite fitness

Mok,

Yeo,

Hong

et al. 2023

Sci. Adv.

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Drug-resistant Plasmodium falciparum parasites have swept across Southeast Asia and now threaten Africa. By implementing a P. falciparum genetic cross using humanized mice, we report the identification of key determinants of resistance to artemisinin (ART) and piperaquine (PPQ) in the dominant Asian KEL1/PLA1 lineage. We mapped k13 as the central mediator of ART resistance in vitro and identified secondary markers. Applying bulk segregant analysis, quantitative trait loci mapping using 34 recombinant haplotypes, and gene editing, our data reveal an epistatic interaction between mutant PfCRT and multicopy plasmepsins 2/3 in mediating high-grade PPQ resistance. Susceptibility and parasite fitness assays implicate PPQ as a driver of selection for KEL1/PLA1 parasites. Mutant PfCRT enhanced susceptibility to lumefantrine, the first-line partner drug in Africa, highlighting a potential benefit of opposing selective pressures with this drug and PPQ. We also identified that the ABCI3 transporter can operate in concert with PfCRT and plasmepsins 2/3 in mediating multigenic resistance to antimalarial agents.

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“…We hypothesize that SMC results in CU5 either being fully protected from infection or, if infected, only having infections with low parasitemia (which may be due to incomplete adherence to the 3-day regimen, or drug resistance). 38 Combined with the lower abundance and density of mosquitoes during the dry season, this then results in lower transmission rates, which leads to a lower incidence. Similar observations have been made in studies evaluating vector control interventions.…”

Section: Discussionmentioning

confidence: 99%

Malaria trends in districts that were targeted and not-targeted for seasonal malaria chemoprevention in children under five years of age in Guinea, 2014–2021

Bisanzio,

Keita,

Camara

et al. 2023

Preprint

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BackgroundSeasonal malaria chemoprevention (SMC) is one of the main interventions recommended by WHO to prevent and reduce childhood malaria. Since 2015, Guinea has implemented SMC targeting children aged 3–59 months (CU5) in districts with high and seasonal malaria transmission.ObjectiveWe assessed the programmatic impact of SMC in Guinea’s context of scaled-up malaria intervention programming by comparing malaria-related outcomes in 14 districts that had (n = 8) or had not (n = 6) been targeted for SMC.MethodUsing routine health management information system data, we calculated the district-level monthly test positivity rate (TPR) and monthly uncomplicated and severe malaria incidence for the whole population and disaggregated age groups (<5yrs and ≥5yrs of age). Changes in malaria indicators through time were analyzed by calculating the district-level compound annual growth rate (CAGR) from 2014 to 2021; we used statistical analyses to describe the time trend of the number of tested clinical cases, TPR, uncomplicated malaria incidence, and severe malaria incidence.ResultThe CAGR of TPR of all age groups was statistically lower in SMC (median = −7.8%, range [IQR] = −9.7%, −5.5%) compared to non-SMC (median = −3.0%, IQR = −3.0%, −1.2%) districts. Similarly, the CAGR in uncomplicated malaria incidence was significantly lower in SMC (median = 1.8%, IQR = −0.9%, 3.5%) compared to non-SMC (median = 11.5%, IQR = 8.8%, 14.0%) districts. For both TPR and uncomplicated malaria incidence the observed difference was also significant age disaggregated. The CAGR of severe malaria incidence showed that all age groups experienced a decline in severe malaria in both SMC and non-SMC districts. However, this decline was significantly higher in SMC (median = −22.3%, IQR= −27.6%, −18.2%) than in non-SMC (median = −5.1%, IQR= - 7.7; −3.6) districts for the entire population, as well as both CU5 and people over 5 years of age.ConclusionOur results provide evidence to support that—even in an operational programming context—adding SMC to the comprehensive package of malaria interventions yields a positive epidemiological impact and results in greater reduction in TPR, as well as the incidence of uncomplicated and severe malaria in CU5.

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Pharmacokinetic considerations in seasonal malaria chemoprevention

Cited by 14 publications

References 41 publications

Malaria trends in districts that were targeted and not-targeted for seasonal malaria chemoprevention in children under 5 years of age in Guinea, 2014–2021

Malaria trends in districts that were targeted and not-targeted for seasonal malaria chemoprevention in children under 5 years of age in Guinea, 2014–2021

Mapping the genomic landscape of multidrug resistance in Plasmodium falciparum and its impact on parasite fitness

Malaria trends in districts that were targeted and not-targeted for seasonal malaria chemoprevention in children under five years of age in Guinea, 2014–2021

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