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Frontiers in Microbiology 2020Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), which is a novel bunyavirus. SFTSV was... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), which is a novel bunyavirus. SFTSV was first isolated from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction in China. Subsequently, it was found to be widely distributed in Southeast Asia (Korea, Japan, and Vietnam). SFTSV can be transmitted not only from ticks but also from domestic animals, companion animals, and humans. Because the case fatality rate of SFTS is high (6-30%), development of specific and effective treatment for SFTS is required. Studies of potential antiviral drugs for SFTS-specific therapy have been conducted on existing or newly discovered agents and , with ribavirin and favipiravir being the most promising candidates. While animal experiments and retrospective studies have demonstrated the limited efficacy of ribavirin, it was also speculated that ribavirin would be effective in patients with a viral load <1 × 10 copies/mL. Favipiravir showed higher efficacy than ribavirin against SFTSV in assays and greater efficacy in animal models, even administrated 3 days after the virus inoculation. Although clinical trials evaluating the efficacy of favipiravir in SFTS patients in Japan are underway, this has yet to be confirmed. Other drugs, including hexachlorophene, calcium channel blockers, 2'-fluoro-2'-deoxycytidine, caffeic acid, amodiaquine, and interferons, have also been evaluated for their inhibitory efficacy against SFTSV. Among them, calcium channel blockers are promising because in addition to their efficacy and , retrospective clinical data have indicated that nifedipine, one of the calcium channel blockers, reduced the case fatality rate by >5-fold. Although further research is necessary to develop SFTS-specific therapy, considerable progress has been achieved in this area. Here we summarize and discuss recent advances in antiviral drugs against SFTSV.
PubMed: 32117168
DOI: 10.3389/fmicb.2020.00150 -
Journal of Chromatography. B,... Aug 2021Amodiaquine is a drug used for treatment of malaria and is often used in combination with artesunate in areas where malaria parasites are still susceptible to...
Amodiaquine is a drug used for treatment of malaria and is often used in combination with artesunate in areas where malaria parasites are still susceptible to amodiaquine. Liquid chromatography tandem-mass spectrometry was used to quantify amodiaquine and its active metabolite, desethylamodiaquine, in plasma samples. A low sample volume of 100 µl, and high-throughput extraction technique using a supported liquid extraction (SLE) technique on an automated liquid handler platform for faster sample processing are some of the advantages of this method. Separation of amodiaquine from desethylamodiaquine was achieved using a reversed phase Zorbax SB-CN 50 mm × 4.6 mm, I.D. 3.5 µm column with acetonitrile and 20 mM ammonium formate with 1% formic acid pH ~ 2.6 (15-85, v/v) as mobile phase. The absolute recoveries of amodiaquine and desethylamodiaquine were 66% to 76%, and their isotope label internal standard were in the range of 73% to 85%. Validation results of the developed method demonstrated intra-batch and inter-batch precisions within the acceptance criteria range of ± 15.0%. There were no matrix or carry-over effects observed. The lower limit of quantification was 1.08 ng/ml for amodiaquine and 1.41 ng/ml for desethylamodiaquine. The method showed robust and accurate performance with high sensitivity. Thus, the validated method was successfully implemented and applied in the evaluation of a clinical trial where participants received artemether-lumefantrine plus amodiaquine twice daily for three days (amodiaquine dose of 10 mg base/kg/day).
Topics: Amodiaquine; Antimalarials; Chromatography, Liquid; High-Throughput Screening Assays; Humans; Limit of Detection; Linear Models; Liquid-Liquid Extraction; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 34364298
DOI: 10.1016/j.jchromb.2021.122887 -
Malaria Journal May 2017In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal.... (Review)
Review
In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.
Topics: Africa South of the Sahara; Malaria; Malaria Vaccines; Seasons; Vaccination; Vaccines, Synthetic
PubMed: 28464937
DOI: 10.1186/s12936-017-1841-9 -
Molecular Therapy : the Journal of the... Feb 2021Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating...
Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2, thus generating better antiviral efficacy. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Sixteen synergistic and eight antagonistic combinations were identified; among 16 synergistic cases, combinations of the US Food and Drug Administration (FDA)-approved drug nitazoxanide with remdesivir, amodiaquine, or umifenovir were most notable, all exhibiting significant synergy against SARS-CoV-2 in a cell model. However, the combination of remdesivir and lysosomotropic drugs, such as hydroxychloroquine, demonstrated strong antagonism. Overall, these results highlight the utility of drug repurposing and preclinical testing of drug combinations for discovering potential therapies to treat COVID-19.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Drug Combinations; Drug Synergism; Humans; Hydroxychloroquine; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33333292
DOI: 10.1016/j.ymthe.2020.12.016 -
The Cochrane Database of Systematic... Jan 2021The World Health Organization (WHO) in 2015 stated atovaquone-proguanil can be used in travellers, and is an option in malaria-endemic areas in combination with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The World Health Organization (WHO) in 2015 stated atovaquone-proguanil can be used in travellers, and is an option in malaria-endemic areas in combination with artesunate, as an alternative treatment where first-line artemisinin-based combination therapy (ACT) is not available or effective. This review is an update of a Cochrane Review undertaken in 2005.
OBJECTIVES
To assess the efficacy and safety of atovaquone-proguanil (alone and in combination with artemisinin drugs) versus other antimalarial drugs for treating uncomplicated Plasmodium falciparum malaria in adults and children.
SEARCH METHODS
The date of the last trial search was 30 January 2020. Search locations for published trials included the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, and LILACS. To include recently published and unpublished trials, we also searched ClinicalTrials.gov, the metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform Search Portal.
SELECTION CRITERIA
Randomized controlled trials (RCTs) reporting efficacy and safety data for atovaquone-proguanil or atovaquone-proguanil with a partner drug compared with at least one other antimalarial drug for treating uncomplicated Plasmodium falciparum infection.
DATA COLLECTION AND ANALYSIS
For this update, two review authors re-extracted data and assessed certainty of evidence. We meta-analyzed data to calculate risk ratios (RRs) with 95% confidence intervals (CI) for treatment failures between comparisons, and for safety outcomes between and across comparisons. Outcome measures include unadjusted treatment failures and polymerase chain reaction (PCR)-adjusted treatment failures. PCR adjustment differentiates new infection from recrudescent infection.
MAIN RESULTS
Seventeen RCTs met our inclusion criteria providing 4763 adults and children from Africa, South-America, and South-East Asia. Eight trials reported PCR-adjusted data to distinguish between new and recrudescent infection during the follow-up period. In this abstract, we report only the comparisons against the three WHO-recommended antimalarials which were included within these trials. There were two comparisons with artemether-lumefantrine, one trial from 2008 in Ethiopia with 60 participants had two failures with atovaquone-proguanil compared to none with artemether-lumefantrine (PCR-adjusted treatment failures at day 28). A second trial from 2012 in Colombia with 208 participants had one failure in each arm (PCR-adjusted treatment failures at day 42). There was only one comparison with artesunate-amodiaquine from a 2014 trial conducted in Cameroon. There were six failures with atovaquone-proguanil at day 28 and two with artesunate-amodiaquine (PCR-adjusted treatment failures at day 28: 9.4% with atovaquone-proguanil compared to 2.9% with artesunate-amodiaquine; RR 3.19, 95% CI 0.67 to 15.22; 1 RCT, 132 participants; low-certainty evidence), although there was a similar number of PCR-unadjusted treatment failures (9 (14.1%) with atovaquone-proguanil and 8 (11.8%) with artesunate-amodiaquine; RR 1.20, 95% CI 0.49 to 2.91; 1 RCT, 132 participants; low-certainty evidence). There were two comparisons with artesunate-mefloquine from a 2012 trial in Colombia and a 2002 trial in Thailand where there are high levels of multi-resistant malaria. There were similar numbers of PCR-adjusted treatment failures between groups at day 42 (2.7% with atovaquone-proguanil compared to 2.4% with artesunate-mefloquine; RR 1.15, 95% CI 0.57 to 2.34; 2 RCTs, 1168 participants; high-certainty evidence). There were also similar PCR-unadjusted treatment failures between groups (5.3% with atovaquone-proguanil compared to 6.6% with artesunate-mefloquine; RR 0.8, 95% CI 0.5 to 1.3; 1 RCT, 1063 participants; low-certainty evidence). When atovaquone-proguanil was combined with artesunate, there were fewer treatment failures with and without PCR-adjustment at day 28 (PCR-adjusted treatment failures at day 28: 2.16% with atovaquone-proguanil compared to no failures with artesunate-atovaquone-proguanil; RR 5.14, 95% CI 0.61 to 43.52; 2 RCTs, 375 participants, low-certainty evidence) and day 42 (PCR-adjusted treatment failures at day 42: 3.82% with atovaquone-proguanil compared to 2.05% with artesunate-atovaquone-proguanil (RR 1.84, 95% CI 0.95 to 3.56; 2 RCTs, 1258 participants, moderate-certainty evidence). In the 2002 trial in Thailand, there were fewer treatment failures in the artesunate-atovaquone-proguanil group compared to the atovaquone-proguanil group at day 42 with PCR-adjustment. Whilst there were some small differences in which adverse events were more frequent in the atovaquone-proguanil groups compared to comparator drugs, there were no recurrent associations to suggest that atovaquone-proguanil is strongly associated with any specific adverse event.
AUTHORS' CONCLUSIONS
Atovaquone-proguanil was effective against uncomplicated P falciparum malaria, although in some instances treatment failure rates were between 5% and 10%. The addition of artesunate to atovaquone-proguanil may reduce treatment failure rates. Artesunate-atovaquone-proguanil and the development of parasite resistance may represent an area for further research.
Topics: Adult; Amodiaquine; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Atovaquone; Cameroon; Child; Colombia; Drug Combinations; Ethiopia; Humans; Malaria, Falciparum; Mefloquine; Proguanil; Randomized Controlled Trials as Topic; Thailand; Treatment Failure
PubMed: 33459345
DOI: 10.1002/14651858.CD004529.pub3 -
Antimicrobial Agents and Chemotherapy Dec 2017Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of... (Clinical Trial)
Clinical Trial
Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda, from subjects presenting in 2016 with malaria from the community or as part of a clinical trial comparing DP chemoprevention regimens. Compared to community isolates, those from trial subjects had lower sensitivities to the aminoquinolines chloroquine, monodesethyl amodiaquine, and piperaquine and greater sensitivities to lumefantrine and mefloquine, an observation consistent with DP selection pressure. Compared to results for isolates from 2010 to 2013, the sensitivities of 2016 community isolates to chloroquine, amodiaquine, and piperaquine improved (geometric mean 50% inhibitory concentrations [IC] = 248, 76.9, and 19.1 nM in 2010 to 2013 and 33.4, 14.9, and 7.5 nM in 2016, respectively [ < 0.001 for all comparisons]), the sensitivity to lumefantrine decreased (IC = 3.0 nM in 2010 to 2013 and 5.4 nM in 2016 [ < 0.001]), and the sensitivity to dihydroartemisinin was unchanged (IC = 1.4 nM). These changes were accompanied by decreased prevalence of transporter mutations associated with aminoquinoline resistance and low prevalence of polymorphisms recently associated with resistance to artemisinins or piperaquine. Antimalarial drug sensitivities are changing in Uganda, but novel genotypes associated with DP treatment failure in Asia are not prevalent.
Topics: Adolescent; Amodiaquine; Antimalarials; Artemisinins; Aspartic Acid Endopeptidases; Child; Child, Preschool; Chloroquine; Drug Resistance; Ethanolamines; Female; Fluorenes; Gene Expression; Humans; Infant; Inhibitory Concentration 50; Lumefantrine; Malaria, Falciparum; Male; Mefloquine; Membrane Transport Proteins; Multidrug Resistance-Associated Proteins; Mutation; Parasitic Sensitivity Tests; Plasmodium falciparum; Protozoan Proteins; Quinolines; Uganda; Young Adult
PubMed: 28923866
DOI: 10.1128/AAC.01516-17 -
Frontiers in Pharmacology 2023Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on...
Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on drug-drug interactions (DDI) about vortioxetine. In this paper, the inhibitory effect of vortioxetine on cytochrome P450 (CYP450) and the type of inhibitory mechanism were investigated in human and rat liver microsomes. We set up an incubation system of 200 μL to measure the metabolism of probe substrates at the present of vortioxetine at 37°C. The concentrations of the metabolites of probe substrates were all measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. It was found no time-dependent inhibition (TDI) of vortioxetine through determination of half-maximal inhibitory concentration (IC) shift values. The enzymes and metabolites involved in this experiment in human and rats were as follows: CYP3A4/CYP3A (midazolam); CYP2B6/CYP2B (bupropion); CYP2D6/CYP2D (dextromethorphan); CYP2C8/CYP2C-1 (amodiaquine); CYP2C9/CYP2C-2 (losartan); and CYP2C19/CYP2C-3 (mephenytoin). We found that vortioxetine competitively inhibited CYP2C19 and CYP2D6 in human liver microsomes (HLMs) with inhibition constant (K) values of 2.17 μM and 9.37 μM, respectively. It was noncompetitive inhibition for CYP3A4 and CYP2C8, and its K values were 7.26 μM and 6.96 μM, respectively. For CYP2B6 and CYP2C9, vortioxetine exhibited the mixed inhibition with K values were 8.55 μM and 4.17 μM, respectively. In RLMs, the type of vortioxetine inhibition was uncompetitive for CYP3A and CYP2D (K = 4.41 and 100.9 μM). The inhibition type was competitive inhibition, including CYP2B and CYP2C-2 (K = 2.87 and 0.12 μM). The inhibition types of CYP2C-1 and CYP2C-3 (K = 39.91 and 4.23 μM) were mixed inhibition and noncompetitive inhibition, respectively. The study of the above mechanism will provide guidance for the safe clinical use of vortioxetine so that the occurrence of DDI can be avoided.
PubMed: 37790811
DOI: 10.3389/fphar.2023.1199548 -
Open Research Africa 2022Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of...
Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of malaria treatment in Africa. Studies have shown that PQ, AQ, and LM resistance may arise independently of predicted modes of action. Protein kinases have emerged as mediators of drug action and efficacy in malaria parasites; however, the link between top druggable kinases with LM, PQ, and AQ resistance remains unclear. Using LM, PQ, or AQ-resistant parasites, we have evaluated the association of choline kinase (CK), pantothenate kinase 1 (PANK1), diacylglycerol kinase (DAGK), and phosphatidylinositol-4 kinase (PI4Kβ), and calcium-dependent protein kinase 1 (CDPK1) with LM, PQ, and AQ resistance in ANKA. We used bioinformatics tools to identify ligand-binding motifs, active sites, and sequence conservation across the different parasites. We then used PCR and sequencing analysis to probe for single nucleotide polymorphisms (SNPs) within the predicted functional motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1. Using qPCR analysis, we finally measured the mRNA amount of PANK1, DAGK, and PI4Kβ at trophozoites and schizonts stages. We reveal sequence conservation and unique ligand-binding motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1 across malaria species. DAGK, PANK1, and PI4Kβ possessed nonsynonymous mutations; surprisingly, the mutations only occurred in the AQr parasites. PANK1 acquired Asn394His while DAGK contained K270R and K292R mutations. PI4Kβ had Asp366Asn, Ser1367Arg, Tyr1394Asn and Asp1423Asn. We show downregulation of PANK1, DAGK, and PI4Kβ in the trophozoites but upregulation at the schizonts stages in the AQr parasites. The selective acquisition of the mutations and the differential gene expression in AQ-resistant parasites may signify proteins under AQ pressure. The role of the mutations in the resistant parasites and the impact on drug responses require further investigations in malaria parasites.
PubMed: 38915420
DOI: 10.12688/openresafrica.13436.1 -
Malaria Journal Feb 2021Evidence of Plasmodium resistance to some of the current anti-malarial agents makes it imperative to search for newer and effective drugs to combat malaria. Therefore,...
BACKGROUND
Evidence of Plasmodium resistance to some of the current anti-malarial agents makes it imperative to search for newer and effective drugs to combat malaria. Therefore, this study evaluated whether the co-administrations of xylopic acid-amodiaquine and xylopic acid-artesunate combinations will produce a synergistic anti-malarial effect.
METHODS
Antiplasmodial effect of xylopic acid (XA: 3, 10, 30, 100, 150 mg kg), artesunate (ART: 1, 2, 4, 8, 16 mg kg), and amodiaquine (AQ: 1.25, 2.5, 5, 10, 20 mg kg) were evaluated in Plasmodium berghei (strain ANKA)-infected mice to determine respective EDs. Artemether/lumefantrine was used as the positive control. XA/ART and XA/AQ were subsequently administered in a fixed-dose combination of their EDs (1:1) and the combination fractions of their EDs (1/2, 1/4, 1/8, 1/16, and 1/32) to determine the experimental EDs (Z). An isobologram was constructed to determine the nature of the interaction between XA/ART, and XA/AQ combinations by comparing Z with the theoretical ED (Z). Bodyweight and 30-day survival post-treatment were additionally recorded.
RESULTS
EDs for XA, ART, and AQ were 9.0 ± 3.2, 1.61 ± 0.6, and 3.1 ± 0.8 mg kg, respectively. The Z, Z and interaction index for XA/ART co-administration was 5.3 ± 2.61, 1.98 ± 0.25, and 0.37, respectively while that of XA/AQ were 6.05 ± 2.0, 1.69 ± 0.42, and 0.28, respectively. The Z for both combination therapies lay significantly (p < 0.001) below the additive isoboles showing XA acts synergistically with both ART and AQ in clearing the parasites. High doses of XA/ART combination significantly (p < 0.05) increased the survival days of infected mice with a mean hazard ratio of 0.40 while all the XA/AQ combination doses showed a significant (p < 0.05) increase in the survival days of infected mice with a mean hazard ratio of 0.27 similar to AL. Both XA/ART and XA/AQ combined treatments significantly (p < 0.05) reduced weight loss.
CONCLUSION
Xylopic acid co-administration with either artesunate or amodiaquine produces a synergistic anti-plasmodial effect in mice infected with P. berghei.
Topics: Amodiaquine; Animals; Antimalarials; Artesunate; Diterpenes, Kaurane; Dose-Response Relationship, Drug; Drug Combinations; Female; Malaria; Mice; Mice, Inbred ICR; Plasmodium berghei
PubMed: 33632233
DOI: 10.1186/s12936-021-03658-6 -
The Lancet. Infectious Diseases Mar 2023Seasonal malaria chemoprevention is used in 13 countries in the Sahel region of Africa to prevent malaria in children younger than 5 years. Resistance of Plasmodium...
Prevalence of Plasmodium falciparum haplotypes associated with resistance to sulfadoxine-pyrimethamine and amodiaquine before and after upscaling of seasonal malaria chemoprevention in seven African countries: a genomic surveillance study.
BACKGROUND
Seasonal malaria chemoprevention is used in 13 countries in the Sahel region of Africa to prevent malaria in children younger than 5 years. Resistance of Plasmodium falciparum to seasonal malaria chemoprevention drugs across the region is a potential threat to this intervention.
METHODS
Between December, 2015, and March, 2016, and between December, 2017, and March, 2018, immediately following the 2015 and 2017 malaria transmission seasons, community surveys were done among children younger than 5 years and individuals aged 10-30 years in districts implementing seasonal malaria chemoprevention with sulfadoxine-pyrimethamine and amodiaquine in Burkina Faso, Chad, Guinea, Mali, Nigeria, Niger and The Gambia. Dried blood samples were collected and tested for P falciparum DNA by PCR. Resistance-associated haplotypes of the P falciparum genes crt, mdr1, dhfr, and dhps were identified by quantitative PCR and sequencing of isolates from the collected samples, and survey-weighted prevalence and prevalence ratio between the first and second surveys were estimated for each variant.
FINDINGS
5130 (17·5%) of 29 274 samples from 2016 and 2176 (7·6%) of 28 546 samples from 2018 were positive for P falciparum on quantitative PCR. Among children younger than 5 years, parasite carriage decreased from 2844 of 14 345 samples (19·8% [95% CI 19·2-20·5]) in 2016 to 801 of 14 019 samples (5·7% [5·3-6·1]) in 2018 (prevalence ratio 0·27 [95% CI 0·24-0·31], p<0·0001). Genotyping found no consistent evidence of increasing prevalence of amodiaquine resistance-associated variants of crt and mdr1 between 2016 and 2018. The dhfr haplotype IRN (consisting of 51Ile-59Arg-108Asn) was common at both survey timepoints, but the dhps haplotype ISGEAA (431Ile-436Ser-437Gly-540Glu-581Ala-613Ala), crucial for resistance to sulfadoxine-pyrimethamine, was always rare. Parasites carrying amodiaquine resistance-associated variants of both crt and mdr1 together with dhfr IRN and dhps ISGEAA occurred in 0·05% of isolates. The emerging dhps haplotype VAGKGS (431Val-436Ala-437Gly-540Lys-581Gly-613Ser) was present in four countries.
INTERPRETATION
In seven African countries, evidence of a significant reduction in parasite carriage among children receiving seasonal malaria chemoprevention was found 2 years after intervention scale-up. Combined resistance-associated haplotypes remained rare, and seasonal malaria chemoprevention with sulfadoxine-pyrimethamine and amodiaquine is expected to retain effectiveness. The threat of future erosion of effectiveness due to dhps variant haplotypes requires further monitoring.
FUNDING
Unitaid.
Topics: Child; Humans; Plasmodium falciparum; Amodiaquine; Haplotypes; Antimalarials; Seasons; Prevalence; Pyrimethamine; Sulfadoxine; Malaria; Malaria, Falciparum; Drug Combinations; Chemoprevention; Nigeria; Tetrahydrofolate Dehydrogenase; Genomics; Drug Resistance
PubMed: 36328000
DOI: 10.1016/S1473-3099(22)00593-X