15 results on '"Erik, Koehne"'
Search Results
2. A call to caution when hydroxychloroquine is given to elderly patients with COVID-19
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Julian J. Gabor, Andrea Kreidenweiss, Stefan Weber, Moaaz Salama, Mihaly Sulyok, Zita Sulyok, Erik Koehne, Meral Esen, Benno Kreuels, Parichehr Shamsrizi, Erwin Biecker, Benjamin Mordmüller, Christoph P. Berg, Stefano Fusco, Carsten Köhler, Stefan Kubicka, Jens Leitlein, Marylyn Addo, Michael Ramharter, Matthias Schwab, Alfred Lennart Bissinger, Thirumalaisamy P. Velavan, Sanjeev Krishna, and Peter G. Kremsner
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COVID-19 ,Hydroxychloroquine ,Contraindications ,Adverse effects ,SARS-CoV-2 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction: Use of hydroxychloroquine in patients with coronavirus disease 2019 (COVID-19) was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk of hydroxychloroquine interactions with co-morbidities and co-medications contributing to detrimental, including fatal, adverse treatment effects. Methods: A retrospective survey was undertaken of health conditions and co-medications of patients with COVID-19 who were pre-screened for enrolment in a randomized, double-blind, placebo-controlled hydroxychloroquine multi-centre trial. Results: The survey involved 305 patients [median age 71 (interquartile range 59–81) years]. The majority of patients (n = 279, 92%) considered for inclusion in the clinical trial were not eligible, mainly due to safety concerns caused by health conditions or co-medications. The most common were QT-prolonging drugs (n = 188, 62%) and haematologic/haemato-oncologic diseases (n = 39, 13%) which prohibited the administration of hydroxychloroquine. In addition, 165 (54%) patients had health conditions and 167 (55%) patients were on co-medications that did not prohibit the use of hydroxychloroquine but had a risk of adverse interactions with hydroxychloroquine. The most common were diabetes (n = 86, 28%), renal insufficiency (n = 69, 23%) and heart failure (n = 58, 19%). Conclusion: The majority of hospitalized patients with COVID-19 had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, hydroxychloroquine should be administered with extreme caution in elderly patients with COVID-19, and only in clinical trials.
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- 2021
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- View/download PDF
3. In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum
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Erik Koehne, Andrea Kreidenweiss, Bayode Romeo Adegbite, Rella Zoleko Manego, Matthew B.B. McCall, Ghyslain Mombo-Ngoma, Ayola Akim Adegnika, Sélidji Todagbé Agnandji, Benjamin Mordmüller, and Jana Held
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Plasmodium falciparum ,Eravacycline ,Tetracycline ,Isopentenyl pyrophosphate ,Malaria ,Microbiology ,QR1-502 - Abstract
Objectives: Eravacycline is a novel synthetic halogenated tetracycline derivative with a broad antibacterial spectrum. Antibiotics, including tetracyclines, have been used for prophylaxis and, more rarely, for the treatment of malaria for several decades. The rise in drug-resistant malaria parasites renders the search for new treatment candidates urgent. We determined the in vitro potency of eravacycline against Plasmodium falciparum and investigated the apicoplast as a potential drug target. Methods: Four tetracyclines, including eravacycline, tetracycline, tigecycline, and doxycycline, and the lincosamide clindamycin, were tested in 3-day and 6-day in vitro susceptibility assays of P. falciparum laboratory strain 3D7 and/or of clinical isolates obtained from 33 P. falciparum infected individuals from Gabon in 2018. Assays with isopentenyl pyrophosphate substitution were performed to investigate whether apicoplast-encoded isoprenoid biosynthesis is inhibited by these antibiotics. Results: Eravacycline showed the highest activity of all tetracyclines tested in clinical isolates in the 3-day and 6-day assays. Substitution of isopentenyl pyrophosphate in vitro using the laboratory strain 3D7 reversed the activity of eravacycline and comparator antibiotics, indicating the apicoplast to be the main target organelle. Conclusions: These results demonstrate the potential of novel antibiotics, and eravacycline, as candidate antimalarial therapies.
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- 2021
- Full Text
- View/download PDF
4. Correction: Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma
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Erik Koehne, Nina Zander, Miriam Rodi, Jana Held, Wolfgang Hoffmann, Rella Zoleko-Manego, Michael Ramharter, Ghyslain Mombo-Ngoma, Peter G. Kremsner, and Andrea Kreidenweiss
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Published
- 2022
5. Monitoring of efficacy, tolerability and safety of artemether–lumefantrine and artesunate–amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon: an open-label clinical trial
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Bayode R. Adegbite, Jean R. Edoa, Yabo J. Honkpehedji, Frejus J. Zinsou, Jean C. Dejon-Agobe, Mirabeau Mbong-Ngwese, Fabrice Lotola-Mougueni, Erik Koehne, Albert Lalremruata, Andrea Kreidenweiss, The T. Nguyen, Jutta Kun, Selidji T. Agnandji, Bertrand Lell, Abdou R. Safiou, Fridia A. Obone Atome, Ghyslain Mombo-Ngoma, Michael Ramharter, Thirumalaisamy P. Velavan, Benjamin Mordmüller, Peter G. Kremsner, and Ayola A. Adegnika
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Malaria ,Artemether–lumefantrine ,Artesunate–amodiaquine ,Efficacy ,Tolerability ,Safety ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (AS–AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. Methods A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS–AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti‑malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. Results Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86–100) and 95% (95% CI 84–99) for AL and AS–AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. Conclusion This study showed that AL and AS–AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True
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- 2019
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6. Monitoring the threatened utility of malaria rapid diagnostic tests by novel high-throughput detection of Plasmodium falciparum hrp2 and hrp3 deletions: A cross-sectional, diagnostic accuracy study
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Andrea Kreidenweiss, Franziska Trauner, Miriam Rodi, Erik Koehne, Jana Held, Lea Wyndorps, Gédéon Prince Manouana, Matthew McCall, Ayola Akim Adegnika, Albert Lalremruata, Peter G. Kremsner, Rolf Fendel, and Thaisa Lucas Sandri
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Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Plasmodium falciparum deficient for hrp2 and hrp3 genes are a threat to malaria management and elimination, since they escape widely used HRP2-based rapid diagnostic tests and treatment. Hrp2/hrp3 deletions are increasingly reported from all malaria endemic regions but are currently only identified by laborious methodologies. Methods: We developed a novel hydrolysis probe-based, quantitative, real-time PCR (4plex qPCR) for detection and discrimination of P. falciparum infection (cytb) and hrp2 and hrp3 gene status, and to control assay validity (btub). A cross-sectional, diagnostic accuracy study was performed in Gabon for assay validation and deletion screening. Findings: In parallel to identification of P. falciparum infection in samples down to 0.05 parasites/µl, the 4plex qPCR enabled specific and valid interrogation of the parasites´s hrp2 and hrp3 genes in one go - even in low parasitemic samples. The assay was precise and robust also when performed in a routine healthcare setting in Gabon. The risk of falsely identifying hrp2 or hrp3 deletion was reduced by 100-fold compared to conventional PCR. Evaluation against microscopy was performed on 200 blood samples collected in Gabon: sensitivity and specificity of 4plex qPCR (cytb) were 100% and 80%, respectively. Stringent testing revealed hrp2 deletion in 2 of 95 P. falciparum positive and validated samples. Interpretation: The novel 4plex qPCR is sensitive, accurate and allows resource-efficient rapid screening. Monitoring and mapping of hrp2/hrp3 deletions is required to identify areas where control strategies may need to be adapted to ensure appropriate patient care and ultimately achieve malaria elimination. Funding: BMBF (03VP00402).
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- 2019
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7. Description of Plasmodium falciparum infections in central Gabon demonstrating high parasite densities among symptomatic adolescents and adults
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Rella Zoleko Manego, Erik Koehne, Andrea Kreidenweiss, Brice Nzigou Mombo, Bayode Romeo Adegbite, Lia Betty Dimessa Mbadinga, Malik Akinosho, Julian Matthewman, Ayola Akim Adegnika, Michael Ramharter, and Ghyslain Mombo-Ngoma
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Malaria ,Parasitaemia ,Adolescents ,Adults ,Gabon ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria remains a public health issue, particularly in sub-Saharan Africa with special features of seriousness in young children and pregnant women. Adolescents and adults are reported to have acquired a semi-immune status and, therefore, present with low parasitaemia. Children are understood to present with a much higher parasitaemia and severe malaria. It is a concern that effective malaria control programmes targeting young children may lead to a delay in the acquisition of acquired immunity and, therefore, causing a shift in the epidemiology of malaria. Prevalence and parasitaemia were explored in adolescents and adults with Plasmodium falciparum infections compared to young children in the area of Lambaréné, Gabon as an indicator for semi-immunity. Methods A cross-sectional study was conducted at the Centre de Recherches Médicales de Lambaréné (CERMEL) during a 6-month period in 2018. Symptomatic patients, of all ages were screened for malaria at health facilities in Lambaréné and Fougamou and their respective surrounding villages in the central region of Gabon. Plasmodium falciparum infections were determined either by rapid diagnostic test (RDT) or by microscopy. Descriptive analysis of data on parasite densities, anaemia, and fever are presented. Results 1589 individuals screened were included in this analysis, including 731 (46%) adolescents and adults. Out of 1377 assessed, the proportion of P. falciparum positive RDTs was high among adolescents (68%) and adults (44%), compared to young children (55%) and school children (72%). Out of 274 participants assessed for malaria by microscopy, 45 (16%) had a parasite count above 10,000/µl of which 9 (20%) were adults. Conclusion This study shows a high rate of P. falciparum infections in adolescents and adults associated with high-level parasitaemia similar to that of young children. Adolescents and adults seem to be an at-risk population, suggesting that malaria programmes should consider adolescents and adults during the implementation of malaria prevention and case management programmes with continuous care, since they also act as reservoirs for P. falciparum.
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- 2019
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8. DNA recovery from archived RDTs for genetic characterization of Plasmodium falciparum in a routine setting in Lambaréné, Gabon
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The Trong Nguyen, Brice Nzigou Mombo, Albert Lalremruata, Erik Koehne, Rella Zoleko Manego, Lia Betty Dimessa Mbadinga, Ayola Akim Adegnika, Selidji Todagbe Agnandji, Bertrand Lell, Peter Gottfried Kremsner, Thirumalaisamy P Velavan, Michael Ramharter, Benjamin Mordmüller, and Ghyslain Mombo-Ngoma
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Malaria ,Plasmodium falciparum ,RDT ,msp1 ,pfcrt ,Gabon ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Rapid diagnostic tests (RDTs) have been described as a source of genetic material to analyse malaria parasites in proof-of-concept studies. The increasing use of RDTs (e.g., in focal or mass screening and treatment campaigns) makes this approach particularly attractive for large-scale investigations of parasite populations. In this study, the complexity of Plasmodium falciparum infections, parasite load and chloroquine resistance transporter gene mutations were investigated in DNA samples extracted from positive RDTs, obtained in a routine setting and archived at ambient temperature. Methods A total of 669 archived RDTs collected from malaria cases in urban, semi-urban and rural areas of central Gabon were used for P. falciparum DNA extraction. Performance of RDTs as a source of DNA for PCR was determined using: (i) amplification of a single copy merozoite surface protein 1 (msp1) gene followed by highly sensitive and automated capillary electrophoresis; (ii) genotyping of the pfcrt gene locus 72–76 using haplotype-specific-probe-based real-time PCR to characterize chloroquine resistance; and, (iii) real-time PCR targeting 18S genes to detect and quantify Plasmodium parasites. Results Out of the 669 archived RDTs, amplification of P. falciparum nucleic materials had a success rate of 97% for 18S real-time PCR, and 88% for the msp1 gene. The multiplicity of infections (MOI) of the whole population was 2.6 (95% CI 2.5–2.8). The highest number of alleles detected in one infection was 11. The MOI decreased with increasing age (β = − 0.0046, p = 0.02) and residence in Lambaréné was associated with smaller MOIs (p
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- 2019
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9. Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma.
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Erik Koehne, Nina Zander, Miriam Rodi, Jana Held, Wolfgang Hoffmann, Rella Zoleko-Manego, Michael Ramharter, Ghyslain Mombo-Ngoma, Peter G Kremsner, and Andrea Kreidenweiss
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundSchistosomiasis is highly prevalent in Africa. Praziquantel is effective against adult schistosomes but leaves prepatent stages unaffected-which is a limit to patient management and elimination. Given the large-scale use of praziquantel, development of drug resistance by Schistosoma is feared. Antimalarials are promising drugs for alternative treatment strategies of Schistosoma infections. Development of drugs with activity against both malaria and schistosomiasis is particularly appealing as schistosome infections often occur concomitantly with malaria parasites in sub-Saharan Africa. Therefore, antiplasmodial compounds were progressively tested against Schistosoma in vitro, in mice, and in a clinical study.ResultsAmongst 16 drugs and 1 control tested, pyronaridine, methylene blue and 5 other antimalarials were highly active in vitro against larval stage schistosomula with a 50% inhibitory concentration below 10 μM. Both drugs were lethal to ex vivo adult worms tested at 30 μM with methylene blue also active at 10 μM. Pyronaridine treatment of mice infected with S. mansoni at the prepatent stage reduced worm burden by 82% and cured 7 out of 12 animals, however in mice adult stages remained viable. In contrast, methylene blue inhibited adult worms by 60% but cure was not achieved. In an observational pilot trial in Gabon in children, the antimalarial drug combination pyronaridine-artesunate (Pyramax) reduced S. haematobium egg excretion from 10/10 ml urine to 0/10 ml urine, and 3 out of 4 children were cured.ConclusionPyronaridine and methylene blue warrant further investigation as candidates for schistosomiasis treatment. Both compounds are approved for human use and evidence for their potential as antischistosomal compounds can be obtained directly from clinical testing. Particularly, pyronaridine-artesunate, already available as an antimalarial drug, calls for further clinical evaluation.Trial registrationClinicalTrials.gov Identifier NCT03201770.
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- 2021
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10. In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum
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Matthew B. B. McCall, Benjamin Mordmüller, Selidji T Agnandji, Erik Koehne, Bayode Romeo Adegbite, Andrea Kreidenweiss, Jana Held, Rella Zoleko Manego, Ayola A. Adegnika, Ghyslain Mombo-Ngoma, Graduate School, APH - Quality of Care, and APH - Global Health
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0301 basic medicine ,Microbiology (medical) ,Tetracycline ,medicine.drug_class ,030106 microbiology ,Immunology ,Antibiotics ,Plasmodium falciparum ,Isopentenyl pyrophosphate ,Tigecycline ,Microbiology ,Eravacycline ,Anti-Bacterial Agents/pharmacology ,Tetracycline/pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,parasitic diseases ,medicine ,Immunology and Allergy ,Animals ,Humans ,Parasites ,030212 general & internal medicine ,Doxycycline ,Apicoplast ,biology ,Plasmodium falciparum/genetics ,biology.organism_classification ,QR1-502 ,Anti-Bacterial Agents ,Malaria ,chemistry ,Tetracyclines ,Tetracyclines/pharmacology ,medicine.drug - Abstract
Objectives Eravacycline is a novel synthetic halogenated tetracycline derivative with a broad antibacterial spectrum. Antibiotics, including tetracyclines, have been used for prophylaxis and, more rarely, for the treatment of malaria for several decades. The rise in drug-resistant malaria parasites renders the search for new treatment candidates urgent. We determined the in vitro potency of eravacycline against Plasmodium falciparum and investigated the apicoplast as a potential drug target. Methods Four tetracyclines, including eravacycline, tetracycline, tigecycline, and doxycycline, and the lincosamide clindamycin, were tested in 3-day and 6-day in vitro susceptibility assays of P. falciparum laboratory strain 3D7 and/or of clinical isolates obtained from 33 P. falciparum infected individuals from Gabon in 2018. Assays with isopentenyl pyrophosphate substitution were performed to investigate whether apicoplast-encoded isoprenoid biosynthesis is inhibited by these antibiotics. Results Eravacycline showed the highest activity of all tetracyclines tested in clinical isolates in the 3-day and 6-day assays. Substitution of isopentenyl pyrophosphate in vitro using the laboratory strain 3D7 reversed the activity of eravacycline and comparator antibiotics, indicating the apicoplast to be the main target organelle. Conclusions These results demonstrate the potential of novel antibiotics, and eravacycline, as candidate antimalarial therapies.
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- 2021
11. Monitoring the threatened utility of malaria rapid diagnostic tests by novel high-throughput detection of Plasmodium falciparum hrp2 and hrp3 deletions: A cross-sectional, diagnostic accuracy study
- Author
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Thaisa Lucas Sandri, Erik Koehne, Matthew B. B. McCall, Miriam Rodi, Andrea Kreidenweiss, Rolf Fendel, Jana Held, Franziska Trauner, Gédéon Prince Manouana, Albert Lalremruata, Ayola A. Adegnika, Lea Wyndorps, and Peter G. Kremsner
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0301 basic medicine ,Research paper ,Plasmodium falciparum ,Protozoan Proteins ,lcsh:Medicine ,Antigens, Protozoan ,Diagnostic accuracy ,Real-Time Polymerase Chain Reaction ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Patient care ,03 medical and health sciences ,0302 clinical medicine ,Malaria elimination ,parasitic diseases ,Humans ,Medicine ,Malaria, Falciparum ,lcsh:R5-920 ,biology ,business.industry ,lcsh:R ,Electrophoresis, Capillary ,Reproducibility of Results ,Diagnostic test ,General Medicine ,medicine.disease ,biology.organism_classification ,Virology ,High-Throughput Screening Assays ,Cross-Sectional Studies ,030104 developmental biology ,Real-time polymerase chain reaction ,Falciparum infection ,030220 oncology & carcinogenesis ,lcsh:Medicine (General) ,business ,Malaria - Abstract
Background Plasmodium falciparum deficient for hrp2 and hrp3 genes are a threat to malaria management and elimination, since they escape widely used HRP2-based rapid diagnostic tests and treatment. Hrp2/hrp3 deletions are increasingly reported from all malaria endemic regions but are currently only identified by laborious methodologies. Methods We developed a novel hydrolysis probe-based, quantitative, real-time PCR (4plex qPCR) for detection and discrimination of P. falciparum infection (cytb) and hrp2 and hrp3 gene status, and to control assay validity (btub). A cross-sectional, diagnostic accuracy study was performed in Gabon for assay validation and deletion screening. Findings In parallel to identification of P. falciparum infection in samples down to 0.05 parasites/µl, the 4plex qPCR enabled specific and valid interrogation of the parasites´s hrp2 and hrp3 genes in one go - even in low parasitemic samples. The assay was precise and robust also when performed in a routine healthcare setting in Gabon. The risk of falsely identifying hrp2 or hrp3 deletion was reduced by 100-fold compared to conventional PCR. Evaluation against microscopy was performed on 200 blood samples collected in Gabon: sensitivity and specificity of 4plex qPCR (cytb) were 100% and 80%, respectively. Stringent testing revealed hrp2 deletion in 2 of 95 P. falciparum positive and validated samples. Interpretation The novel 4plex qPCR is sensitive, accurate and allows resource-efficient rapid screening. Monitoring and mapping of hrp2/hrp3 deletions is required to identify areas where control strategies may need to be adapted to ensure appropriate patient care and ultimately achieve malaria elimination. Funding BMBF (03VP00402).
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- 2019
- Full Text
- View/download PDF
12. Highly tunable thiosulfonates as a novel class of cysteine protease inhibitors with anti-parasitic activity against Schistosoma mansoni
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David J Ward, Andrea Kreidenweiss, Rob M. J. Liskamp, H. van de Langemheen, and Erik Koehne
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Proteases ,Thiosulfonic Acids ,Clinical Biochemistry ,Pharmaceutical Science ,Cysteine Proteinase Inhibitors ,01 natural sciences ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Animals ,Moiety ,Molecular Biology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Schistosoma mansoni ,biology.organism_classification ,Cysteine protease ,0104 chemical sciences ,Amino acid ,010404 medicinal & biomolecular chemistry ,Papain ,Electrophile ,Molecular Medicine ,Cysteine - Abstract
The development of a new class of cysteine protease inhibitors utilising the thiosulfonate moiety as an SH specific electrophile is described. This moiety has been introduced into suitable amino acid derived building blocks, which were incorporated into peptidic sequences leading to very potent i.e. sub micromolar inhibitors of the cysteine protease papain in the same range as the vinyl sulfone based inhibitor K11777. Therefore, their inhibitory effect on Schistosoma mansoni, a human blood parasite, that expresses several cysteine proteases, was evaluated. The homophenylalanine side chain containing compounds 27 - 30 and especially 36 showed promising activities compared with K11777 and warrant further investigations of these peptidic thiosulfonate inhibitors as new potential anti-parasitic compounds.
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- 2019
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13. Pharmacotherapy for artemisinin-resistant malaria
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Andrea Kreidenweiss, Erik Koehne, Jana Held, and Ayola A. Adegnika
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Pharmacology ,biology ,business.industry ,Drug Resistance ,Plasmodium falciparum ,General Medicine ,medicine.disease ,biology.organism_classification ,Virology ,Artemisinins ,Malaria ,Antimalarials ,Pharmacotherapy ,Parasitic disease ,parasitic diseases ,Medicine ,Humans ,Pharmacology (medical) ,Artemisinin ,Malaria, Falciparum ,business ,medicine.drug - Abstract
Malaria, the most devastating parasitic disease, is currently treated with artemisinin-based combination therapies (ACTs). Unfortunately, some ACTs are unable to rapidly clearThis narrative review gives an overview of approved antimalarials and of some compounds in advanced drug development that could be used when an ACT is failing. The selection was based on a literature search in PubMed and WHO notes for malaria treatment.The ACT drug class can still cure malaria in malaria endemic regions. However, the appropriate ACT drug should be chosen considering the background resistance of the partner drug of the local parasite population. Artesunate-pyronaridine, the 'newest' recommended ACT, and atovaquone-proguanil are, so far, effective, and safe treatments for uncomplicated falciparum malaria. Therefore, all available ACTs should be safeguarded from parasite resistance and the development of new antimalarial drug classes needs to be accelerated.
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- 2021
14. Monitoring of efficacy, tolerability and safety of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon: an open-label clinical trial
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Michael Ramharter, Bayode Romeo Adegbite, Mirabeau Mbong-Ngwese, Albert Lalremruata, Peter G. Kremsner, Fabrice Lotola-Mougueni, Fridia A. Obone Atome, Abdou R. Safiou, Selidji T Agnandji, Andrea Kreidenweiss, Benjamin Mordmüller, Yabo Josiane Honkpehedji, Ghyslain Mombo-Ngoma, Jean Claude Dejon-Agobé, Thirumalaisamy P. Velavan, Frejus J. Zinsou, Jean Ronald Edoa, J. F. J. Kun, Ayola A. Adegnika, Bertrand Lell, Erik Koehne, Graduate School, APH - Aging & Later Life, APH - Global Health, AII - Infectious diseases, and Infectious diseases
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Male ,Artemether/lumefantrine ,Protozoan Proteins ,Drug resistance ,Gene mutation ,Artemisinins/therapeutic use ,Plasmodium falciparum/drug effects ,Amodiaquine/therapeutic use ,0302 clinical medicine ,030212 general & internal medicine ,Malaria, Falciparum ,Artemisinin ,Child ,biology ,Artesunate/amodiaquine ,Malaria, Falciparum/drug therapy ,Tolerability ,Artemisinins ,Drug Combinations ,Infectious Diseases ,Child, Preschool ,Protozoan Proteins/genetics ,Falciparum/drug therapy ,Female ,Artemether ,Drug Monitoring ,Safety ,Artemether, Lumefantrine Drug Combination/therapeutic use ,medicine.drug ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Efficacy ,lcsh:RC955-962 ,Plasmodium falciparum ,030231 tropical medicine ,Artesunate–amodiaquine ,lcsh:Infectious and parasitic diseases ,Antimalarials ,03 medical and health sciences ,Internal medicine ,parasitic diseases ,medicine ,Drug Monitoring/statistics & numerical data ,Humans ,lcsh:RC109-216 ,Gabon ,Preschool ,business.industry ,Research ,Lambaréné ,Artemether, Lumefantrine Drug Combination ,Amodiaquine ,Lumefantrine Drug Combination/therapeutic use ,Infant ,biology.organism_classification ,medicine.disease ,Malaria ,Antimalarials/therapeutic use ,Parasitology ,Artemether–lumefantrine ,business - Abstract
Background Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (AS–AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. Methods A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS–AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti‑malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. Results Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86–100) and 95% (95% CI 84–99) for AL and AS–AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. Conclusion This study showed that AL and AS–AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True
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- 2019
15. Description of Plasmodium falciparum infections in central Gabon demonstrating high parasite densities among symptomatic adolescents and adults
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Erik Koehne, Brice Nzigou Mombo, Bayode Romeo Adegbite, Michael Ramharter, Ayola A. Adegnika, Julian Matthewman, Lia Betty Dimessa Mbadinga, Malik Akinosho, Andrea Kreidenweiss, Ghyslain Mombo-Ngoma, and Rella Zoleko Manego
- Subjects
Male ,Pediatrics ,Parasitemia ,Adolescents ,Epidemiology ,Prevalence ,Prospective Studies ,Malaria, Falciparum ,Child ,Aged, 80 and over ,education.field_of_study ,Rapid diagnostic test ,Parasitaemia ,biology ,Middle Aged ,Infectious Diseases ,Child, Preschool ,Female ,Adult ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Adolescent ,lcsh:RC955-962 ,Population ,Plasmodium falciparum ,lcsh:Infectious and parasitic diseases ,Young Adult ,parasitic diseases ,medicine ,Humans ,Adults ,lcsh:RC109-216 ,Gabon ,education ,Aged ,business.industry ,Public health ,Research ,Infant, Newborn ,Infant ,biology.organism_classification ,medicine.disease ,Malaria ,Cross-Sectional Studies ,Parasitology ,Tropical medicine ,business - Abstract
Background Malaria remains a public health issue, particularly in sub-Saharan Africa with special features of seriousness in young children and pregnant women. Adolescents and adults are reported to have acquired a semi-immune status and, therefore, present with low parasitaemia. Children are understood to present with a much higher parasitaemia and severe malaria. It is a concern that effective malaria control programmes targeting young children may lead to a delay in the acquisition of acquired immunity and, therefore, causing a shift in the epidemiology of malaria. Prevalence and parasitaemia were explored in adolescents and adults with Plasmodium falciparum infections compared to young children in the area of Lambaréné, Gabon as an indicator for semi-immunity. Methods A cross-sectional study was conducted at the Centre de Recherches Médicales de Lambaréné (CERMEL) during a 6-month period in 2018. Symptomatic patients, of all ages were screened for malaria at health facilities in Lambaréné and Fougamou and their respective surrounding villages in the central region of Gabon. Plasmodium falciparum infections were determined either by rapid diagnostic test (RDT) or by microscopy. Descriptive analysis of data on parasite densities, anaemia, and fever are presented. Results 1589 individuals screened were included in this analysis, including 731 (46%) adolescents and adults. Out of 1377 assessed, the proportion of P. falciparum positive RDTs was high among adolescents (68%) and adults (44%), compared to young children (55%) and school children (72%). Out of 274 participants assessed for malaria by microscopy, 45 (16%) had a parasite count above 10,000/µl of which 9 (20%) were adults. Conclusion This study shows a high rate of P. falciparum infections in adolescents and adults associated with high-level parasitaemia similar to that of young children. Adolescents and adults seem to be an at-risk population, suggesting that malaria programmes should consider adolescents and adults during the implementation of malaria prevention and case management programmes with continuous care, since they also act as reservoirs for P. falciparum.
- Published
- 2019
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