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- Bakari, Catherine, et al.
(författare)
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Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021
- 2024
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Ingår i: MALARIA JOURNAL. - 1475-2875. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. Methods A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). Results Sequencing success was >= 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. Conclusion This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.
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- Ngasala, Billy, et al.
(författare)
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Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018
- 2024
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Ingår i: MALARIA JOURNAL. - 1475-2875. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania.Methods A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature >= 37.5 degrees C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety.Results A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported.Conclusion This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.
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- Ernst, R. E., et al.
(författare)
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Identification of the ca. 720 Ma Irkutsk LIP and its plume centre in southern Siberia : The initiation of Laurentia-Siberia separation
- 2023
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Ingår i: Precambrian Research. - 0301-9268. ; 394
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Tidskriftsartikel (refereegranskat)abstract
- Widespread 720 Ma magmatism has been linked with the break-up of Rodinia and the onset of the Sturtian ‘Snowball Earth’ event. We report a new U-Pb baddeleyite age from the Baikal dyke subswarm in southern Siberia which increases the known extent of the 720 Ma Irkutsk LIP and confirms a previous hypothesis that the Baikal and Sayan subswarms converge at the southern tip of the Irkutsk promontory. Together they define a mantle plume centre with direct links to the 720 Ma Franklin plume centre of northern Laurentia, thus constraining the paleo-reconstruction of southern Siberia and northern Laurentia. It is inferred that this combined 720 Franklin – Irktusk LIP event is associated with the breakup of southern Siberia from northern Laurentia during fragmentation of the Rodinia supercontinent. Expansion of 720 Ma magmatism into Siberia greatly increases the scale of the Franklin-Irktusk LIP.
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- Savelev, Aleksandr D., et al.
(författare)
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980-970 Ma Sette-Daban event of the Siberian craton : new geochronological and geochemical data, relationship to LIP and potential connection with other LIPs
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Ingår i: International Geology Review. - 0020-6814.
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Tidskriftsartikel (refereegranskat)abstract
- The paper presents new geological, geochronological, geochemical and Nd-Sr isotopic data on the Meso- Neoproterozoic dolerites of the Siberian Craton. New U-Pb baddeleyite and apatite ages of a E-W-trending dyke and two sills from southeastern Siberia are 982 ± 11, 977 ± 7, 970 ± 31 and 972 ± 60 Ma, respectively, extending the area of distribution of the event by more than 100 km to the north. The Sette-Daban intrusions are subalkalic mostly low-Ti dolerites, although high-Ti dolerites have been locally documented as well. Trace element abundances in dolerites vary from typical to E-MORB to OIB with arc-like signatures represented by high Th/Yb and low TiO2/Yb ratios. All dolerite samples display moderately positive εNd(t) values varying from +3.3 to +7.7 and indicating the magmas were derived from a depleted mantle source. E-MORB and OIB intrusions are attributed to the different degree of interaction of magma between the depleted asthenospheric mantle and regions within the sub-continental lithospheric mantle (SCLM) that were metasomatically enriched during earlier subduction events. Available data on Sette-Daban event distribution, composition and duration satisfy the characteristics of a typical Large Igneous Province (LIP). Similar age 1000–950 Ma mafic magmatism is also recognized in the Baltic and Amazonian cratons and can be potentially correlated with the Sette-Daban event.
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