506 results on '"National Malaria Control Programme"'
Search Results
2. P. Falciparum Infection Dynamics and Transmission to Inform Elimination (INDIE-1b)
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Medical Research Council Unit, The Gambia, National Malaria Control Programme, The Gambia, Radboud University Medical Center, University of California, San Francisco, and Institute for Disease Modeling
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- 2022
3. Feasibility, Acceptability and Costs of a Multiple First-lines Artemisinin-based Combination Therapies
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Medicines for Malaria Venture, National Malaria Control Programme (NMCP), Burkina Faso, and Institut de Recherche en Science de la Santé, Burkina Faso
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- 2022
4. Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination (MASSIV)
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Institute of Tropical Medicine, Belgium, National Malaria Control Programme, The Gambia, Liverpool School of Tropical Medicine, Radboud University Medical Center, University of Durham, and Imperial College London
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- 2022
5. Proactive Community Case Management (Pro-CCM) in Rural Madagascar (Pro-CCM)
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Peace Corps, National Malaria Control Programme, Madagascar, United States Agency for International Development (USAID), and Rila Ratovoson, Researcher
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- 2022
6. Insecticide Treated Polyethylene Sheeting for Prevention of Malaria in Emergencies
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ECHO, UNHCR Country Office Freetown, World Health Organization, Wageningen University, London School of Hygiene and Tropical Medicine, National Malaria Control Programme Sierra Leone, and Institut de Recherche pour le Developpement
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- 2011
7. Safety and Effectiveness of Artemisinin-based Combination Therapies (ACTs) With Repeated Treatments for Uncomplicated Falciparum Malaria Over a Three-year Period
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Malawi-Liverpool-Wellcome Trust Clinical Research Programme, National Malaria Control Programme, Malawi, Research for Equity and Community Health Trust, and Sian Roberts / Head of Research Management
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- 2010
8. Lapdap and Coartemether for Uncomplicated Malaria
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Medical Research Council and National Malaria Control Programme, The Gambia
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- 2006
9. Trial of the Effectiveness of AQ/AS, SP/AQ and SP/CQ for Uncomplicated Malaria in Gambian Children
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Medical Research Council and National Malaria Control Programme, The Gambia
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- 2006
10. An Epidemiological Profile of Malaria and its Control in Mainland Tanzania
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National Malaria Control Programme, NMCP, Ifakara Health Institute, (IHI), World Health Organization, (WHO), and University of Oxford-Keanya, UO-Kenya
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Surveillance, monitoring, evaluation - Published
- 2013
11. Malaria Control in Mainland Tanzania
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National Malaria Control Programme, NMCP
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Surveillance, monitoring, evaluation - Published
- 2012
12. Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness
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Sachel Mok, Adama Gansané, Rithea Leang, Clark H. Cunningham, Romaric Nzoumbou-Boko, David A. Fidock, Aline Uwimana, Ioanna Deni, Nina F. Gnädig, Barbara H. Stokes, Marian Warsame, Kelly Rubiano, Leila S. Ross, Olimatou Kolley, Kurt E. Ward, Issa M. Souleymane, Eric Legrand, Frédéric Ariey, Philip J. Rosenthal, Josefine Striepen, Samuel J. Smith, Abdunoor M. Kabanywanyi, Judith Straimer, Jade Bath, Kyra A Schindler, Didier Menard, Mathieu Ndounga, Tim J. Anderson, François Nosten, Claudette Ndayikunda, Tomas Yeo, Satish K. Dhingra, Columbia University Irving Medical Center (CUIMC), Washington University in Saint Louis (WUSTL), Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U1201 (U1201), Unité de Biologie des interactions hôte-parasite (U1201), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Programme National de Lutte Contre le Paludisme au Tchad, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Laboratoire de parasitologie - Laboratory of Parasitology [Bangui], Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalo-Universitaire de Kamenge [Bujumbura, Burundi] (CHUK), Ifakara Health Institute [Dar-es-Salaam, Tanzania], Rwanda Biomedical Center (RBC), National Malaria Control Programme [Sierra Leone], National Malaria Control Programme [Banjul, Gambia], Programme National de Lutte Contre le Paludisme [Brazzaville, Democratic Republic of the Congo], University of Gothenburg (GU), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Mahidol University [Bangkok], Texas Biomedical Research Institute [San Antonio, TX], University of California [San Francisco] (UCSF), University of California, Columbia University Medical Center (CUMC), Columbia University [New York], DAF gratefully acknowledges the US National Institutes of Health (R01 AI109023), the Department of Defense (W81XWH1910086) and the Bill & Melinda Gates Foundation (OPP1201387) for their financial support. BHS was funded in part by T32 AI106711 (PD: D. Fidock). SM is a recipient of a Human Frontiers of Science Program Long-Term Fellowship. CHC was supported in part by the NIH (R01 AI121558, PI: Jonathan Juliano). FN is supported by the Wellcome Trust of Great Britain (Grant ID: 106698). TJCA acknowledges funding support from the NIH (R37 AI048071). DAF and DM gratefully acknowledge the World Health Organization for their funding., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California [San Francisco] (UC San Francisco), University of California (UC), and Menard, Didier
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0301 basic medicine ,QH301-705.5 ,infectious disease ,Science ,030106 microbiology ,Plasmodium falciparum ,malaria ,global health ,P. falciparum ,Biology ,artemisinin resistance ,medicine.disease_cause ,Southeast asian ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,parasitic diseases ,medicine ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Artemisinin ,Biology (General) ,Genotyping ,CRISPR/Cas9 ,Genetics ,Microbiology and Infectious Disease ,Mutation ,General Immunology and Microbiology ,General Neuroscience ,Point mutation ,microbiology ,General Medicine ,medicine.disease ,biology.organism_classification ,3. Good health ,fitness ,Epidemiology and Global Health ,030104 developmental biology ,Infectious disease (medical specialty) ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Medicine ,epidemiology ,ring-stage survival ,[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Malaria ,Research Article ,medicine.drug - Abstract
The emergence of mutant K13-mediated artemisinin (ART) resistance in Plasmodium falciparum malaria parasites has led to widespread treatment failures across Southeast Asia. In Africa, K13-propeller genotyping confirms the emergence of the R561H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere. Using gene editing, we show that R561H, along with C580Y and M579I, confer elevated in vitro ART resistance in some African strains, contrasting with minimal changes in ART susceptibility in others. C580Y and M579I cause substantial fitness costs, which may slow their dissemination in high-transmission settings, in contrast with R561H that in African 3D7 parasites is fitness neutral. In Cambodia, K13 genotyping highlights the increasing spatio-temporal dominance of C580Y. Editing multiple K13 mutations into a panel of Southeast Asian strains reveals that only the R561H variant yields ART resistance comparable to C580Y. In Asian Dd2 parasites C580Y shows no fitness cost, in contrast with most other K13 mutations tested, including R561H. Editing of point mutations in ferredoxin or mdr2, earlier associated with resistance, has no impact on ART susceptibility or parasite fitness. These data underline the complex interplay between K13 mutations, parasite survival, growth and genetic background in contributing to the spread of ART resistance.
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- 2022
13. Genetic diversity of Plasmodium falciparum populations in three malaria transmission settings in Madagascar
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Arsène Ratsimbasoa, Victor Jeannoda, Tovonahary Angelo Rakotomanga, Didier Menard, Rianasoambolanoro Rakotosaona, Fanomezantsoa Ralinoro, Danielle Rakoto, National Malaria Control Programme of Madagascar, Université d'Antananarivo, Centre National d'Application de Recherches Pharmaceutiques [Antananarivo, Madagascar] (CNARP), Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Fianarantsoa, This work was supported by The Global Fund: NSA2 (MDG-M-PSI 635)., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U1201 (U1201), and Unité de Biologie des interactions hôte-parasite (U1201)
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medicine.medical_specialty ,030231 tropical medicine ,RC955-962 ,Plasmodium falciparum ,Zoology ,Population genetics ,Infectious and parasitic diseases ,RC109-216 ,Biology ,Genetic diversity ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Arctic medicine. Tropical medicine ,parasitic diseases ,medicine ,Madagascar ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Allele ,Malaria, Falciparum ,030304 developmental biology ,0303 health sciences ,msp-1 ,Research ,Genetic Variation ,medicine.disease ,biology.organism_classification ,3. Good health ,Malaria ,msp-2 gene ,Infectious Diseases ,Parasitology ,Tropical medicine ,Nested polymerase chain reaction - Abstract
Background Assessment of the genetic diversity of Plasmodium falciparum parasites from various malaria transmission settings could help to define tailored local strategies for malaria control and elimination. Such assessments are currently scarce in Madagascar. The study presented here aimed to bridge this gap by investigating the genetic diversity of P. falciparum populations in three epidemiological strata (Equatorial, Tropical and Fringes) in Madagascar. Methods Two-hundred and sixty-six P. falciparum isolates were obtained from patients with uncomplicated malaria enrolled in clinical drug efficacy studies conducted at health centres in Tsaratanana (Equatorial stratum), Antanimbary (Tropical stratum) and Anjoma Ramartina (Fringes) in 2013 and 2016. Parasite DNA was extracted from blood samples collected before anti-malarial treatment. Plasmodium species were identified by nested PCR targeting the 18 S rRNA gene. The genetic profiles of P. falciparum parasites were defined by allele-specific nested PCR on the polymorphic regions of the msp-1 and msp-2 genes. Results Fifty-eight alleles were detected in the P. falciparum samples tested: 18 alleles for msp-1 and 40 for msp-2. K1 (62.9%, 139/221) and FC27 (69.5%, 114/164) were the principal msp-1 and msp-2 allele families detected, although the proportions of the msp-1 and msp-2 alleles varied significantly between sites. Polyclonal infections were more frequent at sites in the Equatorial stratum (69.8%) than at sites in the Tropical stratum (60.5%) or Fringes (58.1%). Population genetics analyses showed that genetic diversity was similar between sites and that parasite flow within sites was limited. Conclusions This study provides recent information about the genetic diversity of P. falciparum populations in three transmission strata in Madagascar, and valuable baseline data for further evaluation of the impact of the control measures implemented in Madagascar.
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- 2021
14. Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017–2018
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Leah F. Moriarty, Didier Menard, Innocent Valea, Madou Tapsoba, Ousmane Badolo, Paul Sondo, Esperance Ouédraogo, Cheick Saïd Compaoré, Rene Kinda, Adama Gansané, Blami Dao, Isidore Yerbanga, Edwige Soulama, David T. Kangoye, Halidou Tinto, Casimir Tarama, Samuel Tchwenko, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), U.S. President's Malaria Initiative [Atlanta, GA,], Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris], INSERM U1201 (U1201), Unité de Biologie des interactions hôte-parasite (U1201), Institut de Recherche en Sciences de la Santé (IRSS), CNRST, National Malaria Control Programme [Ouagadougou, Burkina Faso], Improving Malaria Care [Ouagadougou, Burkina Faso], Jhpiego [Baltimore], The study was funded by the US President’s Malaria Initiative through the Improving Malaria Care Project., Institut Pasteur [Paris] (IP), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Male ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Artemether/lumefantrine ,Efficacy ,Combination therapy ,lcsh:RC955-962 ,Plasmodium falciparum ,030231 tropical medicine ,Drug Resistance ,Antimalarial ,lcsh:Infectious and parasitic diseases ,law.invention ,Antimalarials ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Dihydroartemisinin/piperaquine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,law ,Internal medicine ,parasitic diseases ,medicine ,Clinical endpoint ,Humans ,lcsh:RC109-216 ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,030212 general & internal medicine ,Malaria, Falciparum ,Artemether-lumefantrine ,Artemisinin ,business.industry ,Research ,Burkina faso ,Artemether, Lumefantrine Drug Combination ,Infant ,medicine.disease ,Artemisinins ,3. Good health ,Clinical trial ,Infectious Diseases ,Child, Preschool ,Quinolines ,Female ,Parasitology ,business ,Malaria ,Dihydroartemisinin-piperaquine ,medicine.drug - Abstract
Background The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy. Methods This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed. Results Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64–83%) in Nanoro, 76% (66–83%) in Gourcy, and 92% (84–96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75–89%) in Gourcy, 89% (81–94%) in Nanoro, and 97% (92–99%) in Niangoloko. No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation. Conclusion The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso. Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311. Date of registration: 8/3/2017 https://pactr.samrc.ac.za/Search.aspx
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- 2021
15. Measuring the impact of seasonal malaria chemoprevention as part of routine malaria control in Kita, Mali
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Fatou Diawara, Abdoulaye Djimde, Mouctar Diallo, Beh Kamate, Laura C. Steinhardt, Issaka Sagara, Diakalia Koné, Alassane Dicko, Halimatou Diawara, Daouda T. Kone, Almahamoudou Mahamar, Jules Mihigo, Tiangoua Traore, Erin Eckert, Aboubacar Sadou, Université des sciences, des techniques et des technologies de Bamako, Université des sciences, des techniques et des technologies de Bamako (USTTB), Malaria Research and Training Center - MRTC [Bamako, Mali], Département d'Epidémiologie des Affections parasitaires, Malaria Research and training center Université de Bamako, Mali, Université de Bamako, Save the Children, Bamako, Mali, National Malaria Control Programme, Ministry of Health and Social Welfare, Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Centre-Université de Bamako, U.S. President’s Malaria Initiative [Antananarivo] (PMI), U.S. President's Malaria Initiative [Atlanta, GA,], Département d'épidémiologie des affections parasitaires (DEAP), Université de Bamako-Malaria Research and Training Center (MRTC)-Facultés de Médecine, de Pharmacie et d'Odonto-Stomatologie-Centre National de la Recherche Scientifique (CNRS), University of Texas at Arlington [Arlington], Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Université de Bamako-Malaria Research and Training Centre, and Lissalde, Claire
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Male ,Veterinary medicine ,Cross-sectional study ,medicine.medical_treatment ,Mali ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Prevalence ,Medicine ,030212 general & internal medicine ,Child ,Anemia ,3. Good health ,Drug Combinations ,Infectious Diseases ,Tolerability ,Child, Preschool ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,cardiovascular system ,Female ,Seasons ,medicine.drug ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Sulfadoxine ,lcsh:RC955-962 ,030231 tropical medicine ,Amodiaquine ,Chemoprevention ,lcsh:Infectious and parasitic diseases ,Antimalarials ,03 medical and health sciences ,Internal medicine ,parasitic diseases ,Humans ,lcsh:RC109-216 ,business.industry ,Research ,Infant ,medicine.disease ,Malaria ,Cross-Sectional Studies ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Tropical medicine ,Parasitology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business - Abstract
Background Seasonal malaria chemoprevention (SMC) is a new strategy recommended by WHO in areas of highly seasonal transmission in March 2012. Although randomized controlled trials (RCTs) have shown SMC to be highly effective, evidence and experience from routine implementation of SMC are limited. Methods A non-randomized pragmatic trial with pre-post design was used, with one intervention district (Kita), where four rounds of SMC with sulfadoxine + amodiaquine (SP + AQ) took place in August–November 2014, and one comparison district (Bafoulabe). The primary aims were to evaluate SMC coverage and reductions in prevalence of malaria and anaemia when SMC is delivered through routine programmes using existing community health workers. Children aged 3–59 months from 15 selected localities per district, sampled with probability proportional to size, were surveyed and blood samples collected for malaria blood smears, haemoglobin (Hb) measurement, and molecular markers of drug resistance in two cross-sectional surveys, one before SMC (July 2014) and one after SMC (December 2014). Difference-in-differences regression models were used to assess and compare changes in malaria and anaemia in the intervention and comparison districts. Adherence and tolerability of SMC were assessed by cross-sectional surveys 4–7 days after each SMC round. Coverage of SMC was assessed in the post-SMC survey. Results During round 1, 84% of targeted children received at least the first SMC dose, but coverage declined to 67% by round 4. Across the four treatment rounds, 54% of children received four complete SMC courses. Prevalence of parasitaemia was similar in intervention and comparison districts prior to SMC (23.4 vs 29.5%, p = 0.34) as was the prevalence of malaria illness (2.4 vs 1.9%, p = 0.75). After SMC, parasitaemia prevalence fell to 18% in the intervention district and increased to 46% in the comparison district [difference-in-differences (DD) OR = 0.35; 95% CI 0.20–0.60]. Prevalence of malaria illness fell to a greater degree in the intervention district versus the comparison district (DD OR = 0.20; 95% CI 0.04–0.94) and the same for moderate anaemia (Hb
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- 2017
16. Efficacy of artesunate–amodiaquine in the treatment of falciparum uncomplicated malaria in Madagascar
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Oméga Raobela, Didier Menard, Fanomezantsoa Ralinoro, Arsène Ratsimbasoa, Valérie Andriantsoanirina, Tovonahary Angelo Rakotomanga, Stéphane Rabearimanana, David Gael Rajaonera, National Malaria Control Programme of Madagascar, Faculté des Sciences - Université d'Antananarivo, Université d'Antananarivo, Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MDG-M-PSI 635/The Global Fund to Fight AID, Tuberculosis and MalariaMDG-M-PSI 1044/The Global Fund to Fight AIDS Tuberculosis and Malaria, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Menard, Didier
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Male ,Artesunate-amodiaquine ,Therapeutic efficacy survey ,Efficacy ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,030212 general & internal medicine ,Artemisinin ,Malaria, Falciparum ,Child ,[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,biology ,Incidence (epidemiology) ,Artesunate/amodiaquine ,Artemisinins ,3. Good health ,Drug Combinations ,Infectious Diseases ,Child, Preschool ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Combination therapy ,Adolescent ,lcsh:RC955-962 ,030231 tropical medicine ,Plasmodium falciparum ,Context (language use) ,Artesunate–amodiaquine ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Antimalarials ,Young Adult ,Internal medicine ,parasitic diseases ,medicine ,Madagascar ,Humans ,lcsh:RC109-216 ,business.industry ,Research ,Amodiaquine ,Infant ,medicine.disease ,biology.organism_classification ,Malaria ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Parasitology ,business - Abstract
International audience; Background: Since 2006, the artemisinin-based combination therapy (ACT) are recommended to treat uncomplicated malaria including non Plasmodium falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine are the first- and second-line treatment in uncomplicated falciparum malaria, respectively. No clinical drug efficacy study has been published since 2009 to assess the efficacy of these two artemisinin-based combinations in Madagascar, although the incidence of malaria cases has increased from 2010 to 2016. In this context, new data about the efficacy of the drug combinations currently used to treat malaria are needed.Methods: Therapeutic efficacy studies evaluating the efficacy of ASAQ were conducted in 2012, 2013 and 2016 among falciparum malaria-infected patients aged between 6 months and 56 years, in health centres in 6 sites representing different epidemiological patterns. The 2009 World Health Organization protocol for monitoring anti-malarial drug efficacy was followed.Results: A total of 348 enrolled patients met the inclusion criteria including 108 patients in 2012 (n = 64 for Matanga, n = 44 for Ampasipotsy), 123 patients in 2013 (n = 63 for Ankazomborona, n = 60 for Anjoma Ramartina) and 117 patients in 2016 (n = 67 for Tsaratanana, n = 50 for Antanimbary). The overall cumulative PCR-corrected day 28 cure rate was 99.70% (95% IC 98.30-99.95). No significant difference in cure rates was observed overtime: 99.02% (95% IC 94.65-99.83) in 2012; 100% (95% IC 96.8-100) in 2013 and 100% (95% IC 96.65-100) in 2016.Conclusion: The ASAQ combination remains highly effective for the treatment of uncomplicated falciparum malaria in Madagascar.
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- 2018
17. Efficacy of artemisinin-based combination therapies and prevalence of molecular markers associated with artemisinin, piperaquine and sulfadoxine-pyrimethamine resistance in Sierra Leone
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Smith, Samuel J., Kamara, Anitta R.Y., Sahr, Foday, Samai, Mohamed, Swaray, Alpha, Ménard, Didier, Warsame, Marian, National Malaria Control Programme [Sierra Leone], College of Medicine and Allied Health Services [Sierra Leone], National Laboratory [Sierre Leone], Connaught Teaching Hospital [Sierra Leone], Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Global Malaria Programme [Genève], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Financialsupport for the study was provided by the Global Fund to Fight AIDS,Tuberculosis and Malaria, and the Bill & Melinda Gates Foundation., Menard, Didier, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Male ,pfdhfr/pfdhps ,Drug Resistance ,Article ,Artesunate–amodiaquine ,Sierra Leone ,Antimalarials ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Sulfadoxine ,parasitic diseases ,Humans ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,pfplasmepsin2 ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,pfk13 ,Infant ,Artemisinins ,Malaria ,Tetrahydrofolate Dehydrogenase ,Child, Preschool ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Mutation ,Quinolines ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Dihydroartemisinin–piperaquine ,Drug Therapy, Combination ,Female ,Artemether–lumefantrine ,[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology - Abstract
Highlights • The evaluated artemisinin combination therapies were highly efficacious for the treatment of uncomplicated malaria. • Pfk13 mutations and Pfplasmepsin2 multiple copies, associated with artemisinin and piperaquine resistance, respectively, were absent. • The very low prevalence of the quintuple mutant detected supports the introduction of intermittent preventive treatment for infants with SP. • The efficacy and molecular markers of the recommended artemisinins and partners drugs should be monitored continuously., Currently, the national malaria control programme (NMCP) of Sierra Leone recommends artesunate–amodiaquine (ASAQ) and artemether–lumefantrine (AL) as first- and second-line treatment for uncomplicated malaria, respectively, and artesunate + sulfadoxine–pyrimethamine (SP) for intermittent preventive treatment during pregnancy and for infants. In 2016, the NMCP conducted a study to assess the clinical and parasitological responses of children under five years to ASAQ, AL and dihydroartemisinin–piperaquine (DHA/PPQ) according to the WHO protocol. Day-0 samples were tested for mutations in the Kelch 13 gene (pfk13) and dihydrofolate reductase/dihydropteroate synthase (pfdhfr/pfdhps) genes associated with artemisinin and SP resistance, respectively, and amplification in the pfplasmepsin2 gene for piperaquine resistance. A total of 295 (ASAQ = 128, AL = 64 and DHA/PPQ = 103) eligible children were enrolled at three sites. PCR-corrected 100% adequate clinical and parasitological response and no parasitaemia on day-3 were observed for all patients in each treatment group. Of the 278 samples with interpretable molecular data, only 2.2% carried non-synonymous pfk13 mutants (A578S, I646T), which are not associated with artemisinin resistance. None of the 103 day-0 samples from the DAH/PPQ group had pfplasmepsin2 gene amplification, confirming the absence of piperaquine resistance. The prevalence of the triple pfdhfr mutant (N51I/C59R/S108N) was close to or reached fixation (97.4–100%). For combined pfdhfr/pfdhps mutation, 55–71% carried the quadruple (N51I/C59R/S108N+A437G) mutant and about 10% the quintuple mutant N51I/C59R/S108N+A437G/K540E. Our findings confirm that ASAQ, AL and DHA/PPQ were highly effective for the treatment of uncomplicated malaria in the study areas, and neither pfk13 validated mutations nor pfplasmepsin2 multiple copies were found. The very low prevalence of the quintuple mutant in this study supports the NMCP’s decision to introduce intermittent preventive treatment for infants with SP in the districts with high malaria transmission.
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- 2018
18. Single low-dose primaquine for blocking transmission of plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa
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Muhindo Mavoko, Htee Khu Naw, Estrella Lasry, Nicholas J. White, Sodiomon B. Sirima, Melissa C. Kapulu, Mores Loolpapit, Marie Claire Henry, Thomas N. Williams, Alfred Ngwa Amambua, Claude Rwagacondo, Rick M. Fairhurst, Nicholas P. J. Day, Joseph Okebe, Umberto D'Alessandro, Mahamadou Diakite, Rindra Randremanana, Mavuto Mukaka, James A. Berkley, Jean-Pierre Van Geertruyden, Charles O Obonyo, Malcolm E. Molyneux, Muna Affara, Philipe Brasseur, Peter G. Kremsner, Pascal Lutumba, Endalamaw Gadisa, Abraham Aseffa, Grace Malenga, Caterina I. Fanello, Grant Dorsey, Karen I. Barnes, Zolia Yah, Jane Achan, Patrice Piola, Kathryn Maitland, Chandy C. John, Davis Nwakanma, Joel J. Jones, W. Robert Taylor, Birgit Schramm, Marie A. Onyamboko, Junior Matangila, Philip Bejon, Geneva University Hospital (HUG), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], KEMRI-Wellcome Trust Research Programme (KWTRP), Imperial College London, University of Oxford [Oxford], Medical Research Council Unit The Gambia (MRC), University of Antwerp (UA), University of Kinshasa (UNIKIN), Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Epicentre [Paris] [Médecins Sans Frontières], Kinshasa Mahidol Oxford Research Unit (KIMORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Ecole de Santé Publique de Kinshasa (KSPH ou ESP), National Malaria Control Programme, Ministry of Health and Social Welfare, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Queen Elizabeth Hospital, University of Liverpool, Kenya Medical Research Institute (KEMRI), Armauer Hansen Research Institute (AHRI), Amref Health Africa [Kenya], African Medical and Research Foundation (AMREF), Centre de Recherche Entomologique de Cotonou (CREC), Ministère de la Santé, University of California [San Francisco] (UCSF), University of California, Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Groupe de recherche action en santé (GRAS), University of Cape Town, University of Tübingen, TNW is supported by a Fellowship from the Wellcome Trust (202800). The KEMRI–Wellcome Trust Research Programme in Kenya is funded through a Strategic Award from the KEMRI–Wellcome Trust Research Programme (203077). RMF was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health. NJW is a Wellcome Trust Principal Fellow., We acknowledge with gratitude the Demographic Health Survey of USAID for permission to download data from their website. This paper is published with permission from the Director of KEMRI., University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of Oxford, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of California [San Francisco] (UC San Francisco), University of California (UC), RANDRIAMANANTSOA, Volatiana Manohisoa, and Wellcome Trust
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Male ,Primaquine ,Antimalarials / therapeutic use ,lcsh:Medicine ,MESH: Dose-Response Relationship, Drug ,MESH: Clinical Protocols ,MESH: Aged, 80 and over ,0302 clinical medicine ,Clinical Protocols ,MESH: Child ,Epidemiology ,030212 general & internal medicine ,Malaria, Falciparum ,Child ,MESH: Plasmodium falciparum ,Aged, 80 and over ,MESH: Aged ,MESH: Middle Aged ,biology ,MESH: Malaria, Falciparum ,Age Factors ,11 Medical And Health Sciences ,General Medicine ,Middle Aged ,MESH: Primaquine ,MESH: Infant ,3. Good health ,MESH: Glucosephosphate Dehydrogenase Deficiency ,Tolerability ,MESH: Young Adult ,Child, Preschool ,Primaquine / administration & dosage ,Female ,[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Research Article ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Plasmodium falciparum ,030231 tropical medicine ,Antimalarials / adverse effects ,Antimalarials ,Malaria, Falciparum / prevention & control ,Young Adult ,03 medical and health sciences ,Pharmacokinetics ,Age-based dosing ,General & Internal Medicine ,Internal medicine ,parasitic diseases ,medicine ,Humans ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,MESH: Africa South of the Sahara ,Dosing ,Africa South of the Sahara ,ddc:613 ,Aged ,MESH: Adolescent ,MESH: Age Factors ,MESH: Humans ,Dose-Response Relationship, Drug ,business.industry ,lcsh:R ,Malaria, Falciparum / transmission ,MESH: Child, Preschool ,Infant ,MESH: Adult ,medicine.disease ,biology.organism_classification ,MESH: Antimalarials ,MESH: Male ,Malaria ,Regimen ,Glucosephosphate Dehydrogenase Deficiency ,Primaquine / adverse effects ,Primaquine / therapeutic use ,Antimalarials / administration & dosage ,Malaria, Falciparum / drug therapy ,Transmission blocking ,Human medicine ,business ,MESH: Female - Abstract
Background In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Methods Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15–0.4 mg PQ base/kg for children aged 1–5 years and 0.15–0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6–11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box–Cox transformation power exponential and tested PQ doses of 1–15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. Results From the Box–Cox transformation power exponential model, five age categories were selected: (i) 6–11 months (n = 39,886, 6.03%), (ii) 1–5 years (n = 261,036, 45.46%), (iii) 6–9 years (n = 20,770, 3.14%), (iv) 10–14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12–0.25), (ii) 0.21 (0.13–0.37), (iii) 0.25 (0.16–0.38), (iv) 0.26 (0.15–0.38) and (v) 0.27 (0.17–0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. Conclusions We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 − 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0990-6) contains supplementary material, which is available to authorized users.
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- 2018
19. Efficacy and safety of artemisinin-based combination therapy, and molecular markers for artemisinin and piperaquine resistance in Mainland Tanzania
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Johannes B. Kataraihya, Renata Mandike, Mwaka A. Kakolwa, Deus S. Ishengoma, Didier Menard, Marian Warsame, Abdunoor M. Kabanywanyi, Celine I. Mandara, Zul Premji, Martha M. Lemnge, Erasmus Kamugisha, Billy Ngasala, Muhidin K. Mahende, Frank Chacky, Ritha Njau, Sigsbert Mkude, Ifakara Health Institute [Dar-es-Salaam, Tanzania], National Institute for Medical Research [Tanzania] (NIMR), Muhimbili University of Health and Allied Sciences, Catholic University of Health and Allied Sciences [Tanzania], National Malaria Control Programme [Dar es Salaam, Tanzanie] (NMCP), World Health Organization Country Office [Dar es Salaam, Tanzanie], Aga Khan University Hospital (AKUH), Nairobi, University of Gothenburg (GU), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Menard, Didier
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0301 basic medicine ,Male ,medicine.medical_treatment ,Tanzania ,chemistry.chemical_compound ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Artemether ,Prospective Studies ,Artemisinin ,Malaria, Falciparum ,Child ,Artemisinins ,3. Good health ,Drug Combinations ,Infectious Diseases ,Child, Preschool ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Quinolines ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Female ,Safety ,medicine.drug ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,Adolescent ,Efficacy ,lcsh:RC955-962 ,030106 microbiology ,030231 tropical medicine ,Plasmodium falciparum ,Dihydroartemisinin ,Amodiaquine ,Lumefantrine ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Antimalarials ,Internal medicine ,Piperaquine ,parasitic diseases ,medicine ,Humans ,lcsh:RC109-216 ,business.industry ,Research ,Artemether, Lumefantrine Drug Combination ,Infant ,Molecular markers ,medicine.disease ,Artemisinin-based combination therapy ,Malaria ,chemistry ,Artesunate ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Parasitology ,business - Abstract
Background Artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment of uncomplicated malaria in most malaria endemic countries, including Tanzania. Unfortunately, there have been reports of artemisinin resistance and ACT failure from South East Asia highlighting the need to monitor therapeutic efficacy of ACT in these countries as recommended by World Health Organization. Methods Open-label single arm studies in mainland Tanzania were conducted in nine sentinel sites in 2011, 2012 and 2015 to assess the efficacy and safety of artemether/lumefantrine (AL) and artesunate/amodiaquine (ASAQ) using 28 days follow-up and dihydroartemisinin/piperaquine (DHAPQ) using 42 days follow-up. Mutations in the propeller domain of the Plasmodium falciparum kelch 13 (k13) gene and amplification of the P. falciparum plasmepsin 2 (pm2) gene, associated with artemisinin and piperaquine (PQ) resistance, were also investigated. Results Of the 428 patients enrolled, 328 patients provided study endpoint. For AL, the PCR corrected per-protocol analysis showed adequate clinical and parasitological response (ACPR) of 90.3% (n = 28; 95% CI 74.2–98.0) in Kyela 2012, 95.7% (n = 22; 95% CI 78.1–99.0) in Chamwino, 100% in Muheza (n = 29; 95% CI 88.1–100), 100% in Nagaga (n = 39; 95% CI 91.0–100) and Kyela 2015 (n = 60; 95% CI 94.0–100). For ASAQ, PCR corrected ACPR of 98% (n = 49; 95% CI 89.4–99.9) and 100% (n = 25; 95% CI 86.3–100) were observed in 2011 in Ujiji and Kibaha, respectively. For DHAPQ, the ACPR was 100% (n = 71; 95% CI 94.9–100). Of the 235 samples with genetic interpretable results, only 7 (3%) had non-synonymous k13 mutations. None of these are candidate or validated markers of artemisinin resistance and all patients carrying these alleles cleared the parasites on day 3. Of the DHAPQ group, 10% (3/29) of the samples with interpretable results had pm2 multiple copies and none of them was associated with treatment failure. Conclusion All the tested ACT in mainland Tanzania were highly efficacious and none of validated k13 mutants associated with artemisinin resistance was observed. However, three isolates with multiple copy numbers of pm2 gene associated with PQ resistance among the limited samples tested successfully calls for further investigation. Trial registration Number ACTRN12615000159550. Registered 18th February 2015, https://www.anzctr.org.au/trial/MyTrial.aspx
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- 2018
20. Low-grade sulfadoxine–pyrimethamine resistance in Plasmodium falciparum parasites from Lubango, Angola
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Filomeno Fortes, Maria de Fátima Ferreira-da-Cruz, Natália Ketrin Almeida-de-Oliveira, Bianca E Gama, Larissa Rodrigues Gomes, Elsa P. S. Kaingona-Daniel, Didier Menard, Cláudio Tadeu Daniel-Ribeiro, Pesquisa em Malária [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centro de Pesquisa, Diagnóstico e Treinamento em Malária [Rio de Janeiro] (CPD-MAL), Hôpital Central António Agostinho Neto [Lubango, Angola], Health Progress and Investigation Network of the Portuguese-Speaking Countries Community [Lisbon] (RIDESMal/CPLP), Instituto Nacional de Câncer [Rio de Janeiro, Brésil], Angolan National Malaria Control Programme (NMCP), National Institute of Public Health [Angola] (NPHI-Angola), Ministério da Saúde [Luanda, Angola]-Ministério da Saúde [Luanda, Angola], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), CTDR and MFFC are recipients of a Research Productivity Fellowship from the National Brazilian Council for Scientific and Technological Development (CNPq) and from the Foundation for Research Support in the State of Rio de Janeiro (Faperj) as 'Cientistas do Nosso Estado'., and We thank all the patients who voluntarily agreed in participate in this work, as well as the Angolan Ministry of Health and FESA (Eduardo dos Santos Foundation).
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0301 basic medicine ,MESH: Sequence Analysis, DNA ,medicine.medical_treatment ,Drug Resistance ,Protozoan Proteins ,DHPS ,MESH: Tetrahydrofolate Dehydrogenase ,Gene mutation ,Polymerase Chain Reaction ,pfdhfr ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Genotype ,Malaria, Falciparum ,MESH: Dihydropteroate Synthase ,MESH: Protozoan Proteins ,MESH: Plasmodium falciparum ,MESH: Malaria, Falciparum ,3. Good health ,MESH: Angola ,Drug Combinations ,Infectious Diseases ,Pyrimethamine ,MESH: Drug Resistance ,medicine.drug ,MESH: Mutation ,Sulfadoxine ,pfdhps ,MESH: Pyrimethamine ,Plasmodium falciparum ,030231 tropical medicine ,030106 microbiology ,Biology ,P. falciparum ,Antimalarials ,03 medical and health sciences ,parasitic diseases ,MESH: Polymorphism, Genetic ,medicine ,Humans ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,MESH: Drug Combinations ,Dihydropteroate Synthase ,Polymorphism, Genetic ,MESH: Humans ,Research ,Haplotype ,MESH: Polymerase Chain Reaction ,Sequence Analysis, DNA ,biology.organism_classification ,Virology ,MESH: Antimalarials ,Sulfadoxine/pyrimethamine ,Malaria ,Tetrahydrofolate Dehydrogenase ,Angola ,Mutation ,Parasitology ,MESH: Sulfadoxine - Abstract
International audience; BACKGROUND: Malaria is a major parasitic disease, affecting millions of people in endemic areas. Plasmodium falciparum parasites are responsible for the most severe cases and its resistance to anti-malarial drugs is notorious. This is a possible obstacle to the effectiveness of intermittent preventive treatment (IPT) based on sulfadoxine-pyrimethamine (SP) cures administrated to pregnant women (IPTp) during their pregnancy. As this intervention is recommended in Angola since 2006, it has assessed, in this country, the molecular profiles in P. falciparum dhfr and dhps, two polymorphic genes associated to pyrimethamine and sulfadoxine resistance, respectively.METHODS: Blood samples from 52 falciparum patients were collected in Lubango, Angola and pfdhfr and pfdhps polymorphisms were analysed using nested-PCR and DNA sequencing.RESULTS: In the pfdhfr gene, the 108N mutation was almost fixed (98 %), followed by 59R (63 %), 51I (46 %), 50R and 164L (2 %, respectively). No 16V/S mutations were found. The most common double mutant genotype was CNRN (59 + 108; 46 %), followed by CICN (51 + 108; 29 %) whereas IRN (51 + 59 + 108; 15 %), CNRNVL (59 + 108 + 164; 2 %) and RICN (50 + 51 + 108; 2 %) triple mutant genotypes were detected. Investigations of the pfdhps gene showed that the 437G mutation was the most prevalent (97 %). Only two and one samples disclosed the 540E (7 %) and the 436A (3 %), respectively. Single mutant SGKAA (437; 86 %) was higher than SGEAA (437 + 540; 7 %) or AGKAA (436 + 437; 3 %) double mutants genotypes. No polymorphism was detected at codons 581G and 613T/S. Combining pfdhfr and pfdhps alleles two triple mutant haplotypes (double mutant in dhfr and single mutant in dhps) were observed: the ACICNVI/SGKAA in 14 (56 %) samples and the ACNRNVI/SGKAA in five (20 %) samples. One quadruple mutant haplotype was detected (ACIRNVI/SGKAA) in six (24 %) P. falciparum samples. No quintuple pfdhfr-pfdhps mutant was noted.CONCLUSION: pfdhfr and pfdhps gene mutations in isolates from Lubango are suggestive of a low-grade SP resistance and IPT for pregnant women and infant based on SP treatment could be effective. Routine molecular studies targeting polymorphism in these two genes need to be routinely conducted at country level.
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- 2016
21. Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial
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Pascal Houzé, Parastou Valeh, Philippe J Guerin, Timothy Sundaygar, Jean-René Kiechel, Gwenaelle Carn, Eric Comte, Richard G. Smith, Elizabeth A. Ashley, Yah Zolia, Loretxu Pinoges, Joel J. Jones, Elisabeth Baudin, Birgit Schramm, Charles S Mazinda, Mehul Dhorda, Vincent Jullien, Yap Boum, Epicentre [Paris] [Médecins Sans Frontières], Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], National Malaria Control Programme, Ministry of Health and Social Welfare, Médecins Sans Frontières, Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Drugs for Neglected Diseases Initiative, Centre for Tropical Medicine, University of Oxford, Drugs for Neglected Diseases Initiative (DNDi) and Médecins Sans Frontières, Switzerland., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), University of Oxford [Oxford], BMC, Ed., Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 )
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Male ,Artemether/lumefantrine ,MESH : Child, Preschool ,MESH : Malaria, Falciparum ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,MESH : Female ,030212 general & internal medicine ,Malaria, Falciparum ,MESH : Artemisinins ,MESH: Treatment Outcome ,education.field_of_study ,MESH : Fluorenes ,MESH: Malaria, Falciparum ,Artesunate/amodiaquine ,MESH : Infant ,MESH: Infant ,Artemisinins ,3. Good health ,[ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Drug Combinations ,MESH : Drug Combinations ,Infectious Diseases ,Treatment Outcome ,Ethanolamines ,Child, Preschool ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Female ,Artemisinin ,Randomized trial ,medicine.drug ,medicine.medical_specialty ,Efficacy ,MESH : Male ,030231 tropical medicine ,Population ,MESH : Treatment Outcome ,Amodiaquine ,Lumefantrine ,MESH : Amodiaquine ,MESH: Ethanolamines ,MESH : Ethanolamines ,03 medical and health sciences ,Antimalarials ,Internal medicine ,parasitic diseases ,MESH: Liberia ,MESH: Artemisinins ,medicine ,Humans ,MESH: Fluorenes ,education ,MESH: Amodiaquine ,MESH: Drug Combinations ,Fluorenes ,MESH: Humans ,business.industry ,Research ,MESH : Humans ,Artemether, Lumefantrine Drug Combination ,MESH: Child, Preschool ,Infant ,MESH : Liberia ,medicine.disease ,Liberia ,MESH: Antimalarials ,MESH: Male ,Surgery ,Malaria ,Regimen ,chemistry ,MESH : Antimalarials ,Parasitology ,business ,MESH: Female - Abstract
Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce. An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured. The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was −3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017). Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended. The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713 , ISRCTN40020296 .
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- 2013
22. Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia
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Gwenaelle Carn, Eric Comte, Elizabeth A. Ashley, Elisabeth Baudin, Richard G. Smith, Loretxu Pinoges, Yah Zolia, Vincent Jullien, Michel Branger, Joel J. Jones, Birgit Schramm, Jean-René Kiechel, Charles S Mazinda, Arnaud Bruneel, Philippe J Guerin, Parastou Valeh, Timothy Sundaygar, Epicentre [Paris] [Médecins Sans Frontières], National Malaria Control Programme, Ministry of Health and Social Welfare, Médecins Sans Frontières, Biochimie Métabolique et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Virologie, Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Drugs for Neglected Diseases Initiative, Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], This work was supported by Drugs for Neglected Diseases Initiative (DNDi) and Médecins Sans Frontières, Switzerland., University of Oxford, BMC, Ed., Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre for Tropical Medicine ( CCVTM ), and University of Oxford [Oxford]-Nuffield Department of Clinical Medicine
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Male ,Artemether/lumefantrine ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,030212 general & internal medicine ,Malaria, Falciparum ,Child ,Artesunate/amodiaquine ,Middle Aged ,Tolerability ,Artemisinins ,3. Good health ,[ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Drug Combinations ,Infectious Diseases ,Ethanolamines ,Child, Preschool ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Vomiting ,Female ,Artemisinin ,medicine.symptom ,Randomized trial ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Nausea ,030231 tropical medicine ,Amodiaquine ,03 medical and health sciences ,Antimalarials ,Young Adult ,Internal medicine ,medicine ,Humans ,Fluorenes ,business.industry ,Research ,Artemether, Lumefantrine Drug Combination ,Infant ,medicine.disease ,Liberia ,Surgery ,Malaria ,Parasitology ,business - Abstract
Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal. Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28. Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p
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23. Analysis of care-seeking pathways and factors influencing early and appropriate care-seeking for malaria patients in the Republic of Guinea: a cross-sectional study.
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Diallo EM, Traore FB, Camara BS, Langlet A, Delamou A, Diallo OO, Gerbaud L, and Camara A
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- Cross-Sectional Studies, Guinea, Female, Humans, Male, Adult, Adolescent, Young Adult, Middle Aged, Child, Preschool, Child, Infant, Aged, Patient Acceptance of Health Care statistics & numerical data, Malaria
- Abstract
Background: Malaria is a major public health issue in Guinea and care-seeking behaviour is dominated by self-medication and delayed access to appropriate care. However early and appropriate care-seeking are essential to control and reduce complicate forms and mortality, particularly for the most vulnerable. This study was conducted to analyse the diagnostic pathway, and the factors associated with early and appropriate care-seeking for malaria patients in the Republic of Guinea., Methods: A cross-sectional study was carried out between December 2022 to March 2023 in nine health districts within health facilities and at community level. The study population was confirmed malaria patients with RDT or microscopy. Kroeger's conceptual framework was used to design the questionnaire. Conventional recourse was defined as using a healthcare facility or community services, early and appropriate care-seeking was defined as within 24 h of symptom onset in a conventional recourse, and care pathway as the sequence of recourses followed by each patient. Sankey alluvial plots were used to represent patients' diagnostic pathways, and logistic regression to identify factors associated with early and appropriate care-seeking., Results: A total of 3300 malaria patients were studied, of which 1632 (49.45%) were female and 1132 (34.30%) were under 5 years of age, with a median age of 23 months. At the time of the survey, 1337 (40.52%), 1423 (43.12%), and 437 (13.85%) of patients were respectively in their first, second and third recourse. A total of 2002 (60.67%) patients had sought care from a conventional recourse as a first line. Of all patients, 1757 (53.25%) had sought care within 24 h, while 28.55% had sought early and appropriate care. In the initial stages of treatment, self-medication was the most common approach, used by 1214 (37.30%). Patients from the health districts of Boffa (Lower Guinea, coastal region) OR = 0.48 95% CI 0.33-0.70, Dabola (Upper Guinea, savanna region) OR = 0.43 95% CI 0.30-0.63 and Labe (Middle Guinea, mountain region) OR = 0.63 CI 95% 0.43-0.91 (p < 0.05) were more likely to delay appropriate care-seeking, when compared to those in Dixinn, (Conakry). However, the under 5-year-old group OR = 1.55 95% CI 1.30-1.85 (p < 0.001) and the availability of a stable monthly household income OR = 4.98 95% CI 3.03, 8.27 (p < 0.001) were positively associated with early and appropriate care seeking., Conclusion: A low rate of early and appropriate care-seeking was observed. Patients sought care through multiple means, often resulting in a delay in adequate management. The results show the need to deploy strategies adapted to the needs of communities., (© 2024. The Author(s).)
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- 2024
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24. Key contributors to malaria elimination in the People's Republic of China: a scoping review.
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Elhassan SIA
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- China epidemiology, Humans, Malaria prevention & control, Malaria epidemiology, Disease Eradication statistics & numerical data
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Malaria continues to cause high levels of morbidity and mortality despite concerted efforts to control the disease. The global burden is predominantly shouldered by countries in which the disease is highly endemic. In juxtaposition, the majority of evidence on progress towards malaria elimination has been documented in countries where baseline transmission was low. A notable exception is the People's Republic of China, in which the last indigenous case of malaria was recorded in 2016 after reporting over 30 million cases across various transmission strata in 1949. This review examined the extent, range, and nature of the literature addressing key contributors to malaria elimination in China. PubMed, Embase, Web of Science, ProQuest, Google Scholar and the WHO website were searched for relevant articles, and the JBI guidelines were followed for evidence selection, data extraction, and presentation of findings. The 17 articles that satisfied the eligibility criteria demonstrated the centrality of high-level political commitment in the elimination of malaria in China. The national malaria strategy was regularly updated to reflect evolving priorities, and the health system building blocks were strengthened to meet strategic targets. A whole-of-society approach to malaria was adopted, with intersectoral, interprovincial, regional, international, and community-mobilizing collaboration mechanisms established. Collaboration with academic institutions resulted in advantageous discoveries such as artemisinin, the current global gold standard for the treatment of malaria. The impact of malaria-specific interventions was augmented by China's economic growth. The findings of the review highlight the importance of adopting a comprehensive approach to malaria control that addresses the structural determinants of ill-health alongside downstream interventions., (© 2024. The Author(s).)
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- 2024
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25. Using the role model approach to optimise caregiver administration of sulfadoxine-pyrimethamine amodiaquine to children aged 3-59 months in Burkina Faso, Chad and Togo: findings from an evaluation.
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Donovan L, Shafique M, Wharton-Smith A, Richardson S, Viganò E, Traore A, Compaoré C, Tounaikok N, Honoré B, Dingamtel N, Awokou F, Sewu E, Tougri G, Diar MSI, Atcha-Oubou T, Ward C, and Baker K
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- Humans, Togo, Burkina Faso, Child, Preschool, Infant, Chad, Female, Male, Focus Groups, Adult, Antimalarials administration & dosage, Antimalarials therapeutic use, Caregivers psychology, Caregivers statistics & numerical data, Drug Combinations, Malaria prevention & control, Pyrimethamine administration & dosage, Pyrimethamine therapeutic use, Sulfadoxine administration & dosage, Sulfadoxine therapeutic use, Amodiaquine administration & dosage, Amodiaquine therapeutic use
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Background: Seasonal malaria chemoprevention (SMC) is a World Health Organization-recommended intervention for the prevention of malaria among children at high risk in areas with seasonal transmission. During the coronavirus disease 2019 (COVID-19) pandemic, SMC drug distribution was rapidly adapted to reduce contact and mitigate the risk of transmission between communities and community distributors, with caregivers administering doses. To address the challenges and find local solutions to improve administration and adherence, the role model approach was designed, implemented and evaluated in selected communities of Burkina Faso, Chad and Togo. This paper describes the results of this evaluation., Methods: Focus group discussions were held with primary caregivers in all three countries to understand their perceptions of the approach's acceptability and feasibility. In Burkina Faso and Togo, household surveys assessed the characteristics of caregivers reached by role model activities. Key indicators on SMC coverage and adherence allowed for an assessment of caregiver engagement outcomes related to participation in activities. Statistical associations between participation in study's activities and caregiver beliefs related to SMC had been tested., Results: The majority of caregivers believed the approach to have a positive effect on drug administration, with most adopting the promoted strategies. Greater involvement of fathers in drug administration and acknowledgement of their joint responsibility was a notable positive outcome. However, several barriers to participation were noted and there was criticism of the group approach. In Burkina Faso and Togo, end-of-round survey results revealed that 98.4% of respondents agreed the approach improved their knowledge and skills in malaria prevention, while 100% expressed a desire to continue practicing the behaviours learned. However, there was a relatively low level of awareness of the approach among communities. Participation was strongly associated with participants' self-reported belief in ease of remembering to administer, and ease of administering, SMC medicines., Conclusion: Caregivers perceived the role model approach to be beneficial in aiding drug administration, with other positive impacts also reported. Replication and scale-up should utilize the most popular communication channels and existing community structures to ensure activities are promoted effectively. A mixture of group and one-on-one approaches should be used where appropriate and feasible., (© 2024. The Author(s).)
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- 2024
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26. Prevalence of mutations associated with artemisinin partial resistance and sulfadoxine-pyrimethamine resistance in 13 regions in Tanzania in 2021: a cross-sectional survey.
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Juliano JJ, Giesbrecht DJ, Simkin A, Fola AA, Lyimo BM, Pereus D, Bakari C, Madebe RA, Seth MD, Mandara CI, Popkin-Hall ZR, Moshi R, Mbwambo RB, Niaré K, MacInnis B, Francis F, Mbwambo D, Garimo I, Chacky F, Aaron S, Lusasi A, Molteni F, Njau RJA, Nhiga SL, Mohamed A, Bailey JA, and Ishengoma DS
- Abstract
Background: The emergence of the artemisinin partial resistance (ART-R) mutation in the Plasmodium falciparum kelch13 gene (k13), Arg561His, in Rwanda and the regional presence of polymorphisms affecting sulfadoxine-pyrimethamine have raised concern in neighbouring Tanzania. The goal of this study was to assess the status of antimalarial resistance in Tanzania, with a focus on the border with Rwanda, to understand the distribution of the Arg561His mutation, partner drug resistance, and resistance to chemoprevention drugs., Methods: In this cross-sectional survey, capillary dried blood spots were collected from malaria positive asymptomatic individuals in the community and symptomatic individuals in health facilities aged 6 months and older, in 13 regions of mainland Tanzania from Jan 31 to June 26, 2021. Exclusion criteria included residence of the areas other than the target sites, presenting to the health facility for care and treatment of conditions other than malaria, and not providing informed consent. Samples were assessed for antimalarial resistance polymorphisms and genetic relatedness using molecular inversion probes targeting P falciparum and short-read whole-genome sequencing. The primary outcome was the prevalence of molecular markers of antimalarial resistance at the region level, as well as at the district level in Kagera, a region in the northwest of the country at the border with Rwanda., Findings: 6855 (88·1%) of 7782 capillary dried blood spot samples collected were successfully genotyped. The overall prevalence of k13 Arg561His in Kagera was 7·7% (90% CI 6·0-9·4; 50 of 649), with the highest prevalence in the districts near the Rwandan border (22·8% [31 of 136] in Karagwe, 14·4% [17 of 118]) in Kyerwa, and 1·4% [two of 144] in Ngara). k13 Arg561His was uncommon in the other regions. Haplotype analysis suggested that some of these parasites are related to isolates collected in Rwanda in 2015, supporting regional spread of Arg561His. However, a novel k13 Arg561His haplotype was observed, potentially indicating a second origin in the region. Other validated k13 resistance polymorphisms (one Arg622Ile and two Ala675Val isolates) were also identified. A region of prevalent dihydrofolate reductase Ile164Leu mutation, associated with sulfadoxine-pyrimethamine resistance, was also identified in Kagera (15·2% [12·6-17·8%]; 80 of 526). The mutant crt Lys76Thr mutation, associated with chloroquine and amodiaquine resistance, was uncommon, occurring only in 75 of 2861 genotyped isolates, whereases the wild-type mdr1 Asn86Tyr allele, associated with reduced sensitivity to lumefantrine, was found in 99·7% (3819 of 3830) of samples countrywide., Interpretation: These findings show that the k13 Arg561His mutation is common in northwest Tanzania and that multiple emergences of ART-R, similar as to what was seen in southeast Asia, have occurred. Mutations associated with high levels of sulfadoxine-pyrimethamine resistance are common. These results raise concerns about the long-term efficacy of artemisinin and chemoprevention antimalarials in the region. Understanding how multiple emergences interact with drivers of regional spread is essential for combating ART-R in Africa., Funding: This study was funded by the Bill & Melinda Gates Foundation and the National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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27. Malaria burden and residual transmission: two thirds of mosquito bites may not be preventable with current vector control tools on Bioko Island, Equatorial Guinea.
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Ooko M, Bela NR, Leonard M, Maye VON, Efiri PBE, Ekoko W, Rivas MR, Galick DS, DeBoer KR, Donfack OT, Guerra CA, García GA, and Kleinschmidt I
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Objectives: This study assesses exposure to malaria vector mosquitos that is nonpreventable through use of nets, the contribution of outdoor and indoor biting towards residual vector exposure, and the risk factors for being bitten and for being infected with malaria parasites on Bioko Island, Equatorial Guinea., Methods: Human behavior and malaria infection data were collected from 13,735 randomly selected residents during cross-sectional surveys, concomitantly with entomological human landing catches, indoors and outdoors, in 20 locations on the Island. Self-reported time of going indoors, going to bed and whether using a net were analyzed to impute for each respondent the number of bites received outdoors and indoors during the night before the survey., Results: On average, each person received 2.7 (95% CI: 2.6-2.8) bites per night outdoors, 8.5 (8.3 to 8.7) bites indoors if not using a net, and 4.7 (4.5 to 4.8) bites indoors if using a net. Malaria infection was associated with more bites, regardless of whether received indoors or outdoors. Older age, male gender, not using a net, rural location, and going indoors later increased the risk of being bitten. The proportion of bites not averted by using a net was estimated as 66% (61 to 71)., Conclusions: A large proportion of biting, mostly indoors, may not be preventable by bednets. Tools targeting indoor biting should be prioritized in Bioko. Novel vector control tools are urgently needed to reduce overall exposure to mosquito bites., Competing Interests: Declarations of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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28. WHO antenatal care policy and prevention of malaria in pregnancy in sub-Saharan Africa.
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Olapeju B, Bride M, Gutman JR, Wolf K, Wabwire S, Atobrah D, Babanawo F, Akrofi OO, Atta-Obeng C, Soro BK, Touré F, Shekarau E, and Hendrickson ZM
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- Humans, Female, Pregnancy, Africa South of the Sahara, Adult, Young Adult, Adolescent, Middle Aged, Pregnancy Complications, Parasitic prevention & control, Prenatal Care statistics & numerical data, Malaria prevention & control, World Health Organization, Antimalarials therapeutic use, Antimalarials administration & dosage, Health Policy
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Background: The WHO 2016 antenatal care (ANC) policy recommends at least eight antenatal contacts during pregnancy. This study assessed ANC8 uptake following policy implementation and explored the relationship between ANC attendance and intermittent preventive treatment in pregnancy (IPTp) coverage in sub-Saharan Africa following the rollout of the World Health Organization (WHO) 2016 ANC policy, specifically, to assess differences in IPTp uptake between women attending eight versus four ANC contacts., Methods: A secondary analysis of data from 20 sub-Saharan African countries with available Demographic Health and Malaria Indicator surveys from 2018 to 2023 was performed. The key variables were the number of ANC contacts and IPTp doses received during a participant's last completed pregnancy in the past two years. Pooled crude and multivariable logistic regression models were used to explore factors associated with attendance of at least four or eight ANC contacts as well as receipt of at least three doses of IPTp during pregnancy., Results: Overall, only a small proportion of women (median = 3.9%) completed eight or more ANC contacts (ANC8 +). Factors significantly associated with increased odds of ANC8 + included early ANC attendance (AOR: 4.61: 95% CI 4.30-4.95), literacy (AOR: 1.20; 95% CI 1.11-1.29), and higher wealth quintile (AOR: 3.03; 95% CI 2.67-3.44). The pooled estimate across all countries showed a very slight increase in the odds of IPTp3 + among women with eight (AOR: 1.06; 95% CI 1.00-1.12) compared to those with four contacts. In all but two countries, having eight instead of four ANC contacts did not confer significantly greater odds of receiving three or more doses of IPTp (IPTp3 +), except in Ghana (AOR: 1.67; 95% CI 1.38-2.04) and Liberia (AOR: 1.43; 95% CI 1.18-1.72)., Conclusion: Eight years after the WHO ANC policy recommendation, all countries still had sub-optimal ANC8 + coverage rates. This paper is a call to action to actualize the vision of the WHO and the global malaria community of a malaria free world. Policies to improve ANC and IPTp coverage should be operationalized with clear actionable guidance and local ownership. Study findings can be used to inform multi-level policy, programmatic, and research recommendations to optimize ANC attendance and malaria in pregnancy prevention, thus improving maternal and child health outcomes, including the reduction of malaria in pregnancy., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2024
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29. Mass drug administration to reduce malaria incidence in a low-to-moderate endemic setting: short-term impact results from a cluster randomised controlled trial in Senegal.
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Ba Konko Ciré EH, Roh ME, Diallo A, Gadiaga T, Seck A, Thiam S, Gaye S, Diallo I, Lo AC, Diouf E, Ba OG, Gueye AB, Fogelson A, Wu X, Milligan P, Kibuka T, Hama M, Eckert E, Thwing J, Bennett A, Gosling R, Hwang J, Sene D, Ba F, Cissé B, Sturm-Ramirez K, Hsiang MS, and Ndiaye JL
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Background: In Africa, the scale-up of malaria control interventions, including seasonal malaria chemoprevention (SMC), has dramatically reduced malaria burden, but progress toward malaria elimination has stalled. We evaluated mass drug administration (MDA) as a strategy to accelerate reductions in malaria incidence in Senegal., Methods: We conducted an open-label, cluster-randomised controlled trial in a low-to-moderate transmission setting of Tambacounda, Senegal. Eligible villages had a population size between 200-800. All villages received pyrethroid-piperonyl butoxide bednets and proactive community case management of malaria at baseline. Sixty villages were randomised 1:1 to either three cycles of MDA with dihydroartemisinin-piperaquine+single-low dose primaquine administered to individuals aged ≥3 months, six-weeks apart starting the third week of June (intervention), or standard-of-care, which included three monthly cycles of SMC with sulfadoxine-pyrimethamine+amodiaquine administered to children aged 3-120 months starting end of July (control). MDA and SMC were delivered door-to-door. The primary outcome was clinical malaria incidence in all ages assessed during the peak transmission season (July-December), the year after intervention. Here, we report safety, coverage, and impact outcomes during the intervention year. The trial is registered at ClinicalTrials.Gov (NCT04864444)., Findings: Between June 21, 2021 and October 3, 2021, 6505, 7125, and 7250 participants were administered MDA and 3202, 3174, and 3146 participants were administered SMC across cycles. Coverage of ≥1 dose of MDA drugs was 79%, 82%, and 83% across cycles. During the transmission season of the intervention year, MDA was associated with a 55% [95% CI: 28%-72%] lower incidence of malaria compared to control (MDA: 93 cases/1000 population; control: 173 cases/1000 population). No serious adverse events were reported in either arm., Interpretation: In low-to-moderate malaria transmission settings with scaled-up malaria control interventions, MDA with dihydroartemisinin-piperaquine+single-low dose primaquine is effective and well-tolerated for reducing malaria incidence. Further analyses will focus on the sustainability of this reduction., Funding: United States President's Malaria Initiative., Competing Interests: Declaration of interests The study was funded by the US President’s Malaria Initiative. MER is supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (Award Number K99HD111572). JH and ABG receive salary support from the US President’s Malaria Initiative. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health, US Centers of Disease Control and Prevention, and the US Agency for International Development.
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- 2024
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30. Malaria prevalence and transmission in the Zakpota sub-district of central Benin: baseline characteristics for a community randomised trial of a new insecticide for indoor residual spraying.
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Govoetchan R, Fongnikin A, Hueha C, Ahoga J, Boko C, Syme T, Issiakou R, Agbevo A, Aikpon R, Small G, Snetselaar J, Ossè R, Tokponnon F, Padonou GG, and Ngufor C
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- Benin epidemiology, Humans, Animals, Prevalence, Child, Preschool, Female, Male, Infant, Insecticide Resistance, Pyrethrins pharmacology, Insecticides pharmacology, Mosquito Control methods, Mosquito Vectors drug effects, Mosquito Vectors parasitology, Anopheles drug effects, Anopheles parasitology, Anopheles physiology, Malaria transmission, Malaria prevention & control, Malaria epidemiology
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Background: Malaria transmission is known to be perennial and heterogeneous in Benin. Studies assessing local malaria prevalence, transmission levels and vector characteristics are critical for designing, monitoring and evaluating new vector control interventions in community trials. We conducted a study in the Zakpota sub-district of central Benin to collect baseline data on household characteristics, malaria prevalence, vector characteristics and transmission dynamics in preparation for a randomised controlled trial to evaluate the community impact of VECTRON™ T500, a new broflanilide indoor residual spraying (IRS) product., Methods: A total of 480 children under 5 years of age from the 15 villages of the sub-district were tested for malaria by rapid diagnostic tests (RDTs). Mosquitoes were collected by human landing catches (HLCs), pyrethrum spray catches (PSCs) and Centers for Disease Control and Prevention miniature light traps (CDC-LTs) in selected houses in each village to assess vector density, composition, vector infectivity and prevalence of insecticide resistance markers. Bioassays were performed to detect vector susceptibility to pyrethroids, broflanilide (6 µg/bottle) and clothianidin (90 µg/bottle)., Results: A total of 9080 households were enumerated in the 15 study villages. Insecticide-treated net (ITN) usage was > 90%, with 1-2 ITNs owned per household. Houses were constructed mainly with cement (44%) and mud (38%) substrates or a mixture of cement and mud (18%), and 60% of them had open eaves. The overall prevalence of P. falciparum infection was 19% among surveyed children: 20% among females and 18% among males. The haemoglobin rate showed an anaemia (< 11 g/dl) prevalence of 66%. Anopheles coluzzii and An. gambiae sensu stricto (s.s.) were the two vector species present at an overall proportion of 46% versus 54%, respectively. The human biting rate was 2.3 bites per person per night (b/p/n) and biting occurred mostly indoors compared with outdoors (IRR = 0.776; P = 0.001). The overall proportion of outdoor biting was 44% and exceeded indoor biting in three villages. The sporozoite rate was 2% with a combined yearly entomological inoculation rate (EIR) of 16.1 infected bites per person per year (ib/p/y). There was great variability in malaria transmission risk across the villages, with EIR ranging from 0 to 29.3 ib/p/y. The vector population showed a high intensity of resistance to pyrethroids across the study villages but was largely susceptible to broflanilide and clothianidin., Conclusions: This study found high levels of malaria prevalence, vector density and transmission in the Zakpota sub-district despite the wide use of insecticide-treated nets. The vector population was mostly indoor resting and showed a high intensity of pyrethroid resistance but was generally fully susceptible to broflanilide. These findings demonstrated the suitability of the study area for the assessment of VECTRON™ T500 in a community randomised trial., (© 2024. The Author(s).)
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- 2024
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31. Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time.
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Ndiaye YD, Wong W, Thwing J, Schaffner SF, Brenneman KV, Tine A, Diallo MA, Deme AB, Sy M, Bei AK, Thiaw AB, Daniels R, Ndiaye T, Gaye A, Ndiaye IM, Toure M, Gadiaga N, Sene A, Sow D, Garba MN, Yade MS, Dieye B, Diongue K, Zoumarou D, Ndiaye A, Gomis JF, Fall FB, Ndiop M, Diallo I, Sene D, Macinnis B, Seck MC, Ndiaye M, Ngom B, Diedhiou Y, Mbaye AM, Ndiaye L, Sy N, Badiane AS, Hartl DL, Wirth DF, Volkman SK, and Ndiaye D
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- Senegal, Retrospective Studies, Humans, Malaria, Falciparum parasitology, Malaria, Falciparum epidemiology, Polymorphism, Single Nucleotide, Protozoan Proteins genetics, Haplotypes, Membrane Transport Proteins genetics, Plasmodium falciparum drug effects, Plasmodium falciparum genetics, Drug Resistance genetics, Antimalarials pharmacology, Antimalarials therapeutic use, Mutation
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Background: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance., Methods: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics., Results: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014., Discussion (conclusion): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention., (© 2024. The Author(s).)
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- 2024
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32. High prevalence and risk of malaria among asymptomatic individuals from villages with high prevalence of artemisinin partial resistance in Kyerwa district of Kagera region, north-western Tanzania.
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Mandai SS, Francis F, Challe DP, Seth MD, Madebe RA, Petro DA, Budodo R, Kisambale AJ, Chacha GA, Moshi R, Mbwambo RB, Pereus D, Bakari C, Aaron S, Mbwambo D, Lusasi A, Kajange S, Lazaro S, Kapologwe N, Mandara CI, and Ishengoma DS
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- Tanzania epidemiology, Male, Prevalence, Female, Humans, Cross-Sectional Studies, Child, Child, Preschool, Adolescent, Adult, Young Adult, Middle Aged, Infant, Drug Resistance, Malaria epidemiology, Aged, Malaria, Falciparum epidemiology, Malaria, Falciparum parasitology, Risk Factors, Plasmodium falciparum drug effects, Artemisinins pharmacology, Artemisinins therapeutic use, Antimalarials therapeutic use, Antimalarials pharmacology
- Abstract
Background: Although Tanzania adopted and has been implementing effective interventions to control and eventually eliminate malaria, the disease is still a leading public health problem, and the country experiences heterogeneous transmission. Recent studies reported the emergence of parasites with artemisinin partial resistance (ART-R) in Kagera region with high prevalence (> 10.0%) in two districts of Karagwe and Kyerwa. This study assessed the prevalence and predictors/risk of malaria infections among asymptomatic individuals living in a hyperendemic area where ART-R has emerged in Kyerwa District of Kagera region, north-western Tanzania., Methods: This was a community-based cross-sectional survey which was conducted in July and August 2023 and involved individuals aged ≥ 6 months from five villages in Kyerwa district. Demographic, anthropometric, clinical, parasitological, type of house inhabited and socio-economic status (SES) data were collected using electronic capture tools run on Open Data Kit (ODK) software. Predictors/risks of malaria infections were determined by univariate and multivariate logistic regression, and the results were presented as crude (cORs) and adjusted odds ratios (aORs), with 95% confidence intervals (CIs)., Results: Overall, 4454 individuals were tested using rapid diagnostic tests (RDTs), and 1979 (44.4%) had positive results. The prevalence of malaria infections ranged from 14.4% to 68.5% and varied significantly among the villages (p < 0.001). The prevalence and odds of infections were significantly higher in males (aOR = 1.28, 95% CI 1.08 -1.51, p = 0.003), school children (aged 5-≤10 years (aOR = 3.88, 95% CI 3.07-4.91, p < 0.001) and 10-≤15 years (aOR = 4.06, 95% CI 3.22-5.13, p < 0.001)) and among individuals who were not using bed nets (aOR = 1.22, 95% CI 1.03-1.46, p = 0.024). The odds of malaria infections were also higher in individuals with lower SES (aOR = 1.42, 95% CI 1.17-1.72, p < 0.001), and living in houses without windows (aOR = 2.08, 95% CI 1.46-2.96, p < 0.001), partially open (aOR = 1.33, 95% CI 1.11-1.58, p = 0.002) or fully open windows (aOR = 1.30, 95%CI 1.05-1.61, p = 0.015)., Conclusion: The five villages had a high prevalence of malaria infections and heterogeneity at micro-geographic levels. Groups with higher odds of malaria infections included school children, males, and individuals with low SES, living in poorly constructed houses or non-bed net users. These are important baseline data from an area with high prevalence of parasites with ART-R and will be useful in planning interventions for these groups, and in future studies to monitor the trends and potential spread of such parasites, and in designing a response to ART-R., (© 2024. The Author(s).)
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- 2024
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33. Health workers' adherence to malaria case management protocols in Northern Sudan: a qualitative study.
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Khalid Mohamed S, Khalid Mohamed D, Ahmed K, Saad F, and Zurovac D
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- Sudan, Humans, Qualitative Research, Guideline Adherence statistics & numerical data, Male, Focus Groups, Female, Adult, Malaria drug therapy, Malaria diagnosis, Health Personnel, Case Management, Antimalarials therapeutic use
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Background: Nonadherence to national standards for malaria diagnosis and treatment has been reported in Sudan. In this study, qualitative research examined the clinical domains of nonadherence, factors influencing nonadherent practices and health workers' views on how to improve adherence., Methods: In September 2023, five Focus Group Discussions (FGDs) were undertaken with 104 health workers from 42 health facilities in Sudan's Northern State. The participants included medical assistants, doctors, nurses, laboratory personnel, pharmacists and public health officers. The FGDs followed a semi-structured guide reflecting the national malaria case management protocol. Qualitative thematic analysis was performed., Results: Nonadherent practices included disregarding parasitological test results, suboptimal paediatric artemether-lumefantrine (AL) dosing, lack of counselling, use of prohibited artemether injections for uncomplicated and severe malaria, artesunate dose approximations and suboptimal preparations, lack of AL follow on treatment for severe malaria; and rare use of primaquine for radical Plasmodium vivax treatment and dihydroartemisinin-piperaquine as the second-line treatment for uncomplicated malaria. Factors influencing nonadherence included stock-outs of anti-malarials and RDTs; staff shortages; lack of training, job aids and supervision; malpractice by specialists; distrust of malaria microscopy and RDTs; and patient pressure for diagnosis and treatment. Health workers recommended strengthening the supply chain; hiring personnel; providing in-service protocol training including specialists; establishing external quality assurance for malaria diagnosis; and providing onsite supportive supervision and public health campaigns., Conclusions: This study revealed a broad spectrum of behavioural and systemic challenges in malaria management among frontline health workers in Northern Sudan, including nonadherence to protocols due to resource shortages, training gaps, a lack of supportive supervision and patient pressure. These insights, including health workers' views about improvements, will inform evidence-based interventions by Sudan's National Malaria Control Programme to improve health systems readiness and the quality of malaria case management., (© 2024. The Author(s).)
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- 2024
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34. Urbanization and malaria have a contextual relationship in endemic areas: A temporal and spatial study in Ghana.
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Savi MK, Pandey B, Swain A, Lim J, Callo-Concha D, Azondekon GR, Wahjib M, and Borgemeister C
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In West Africa, malaria is one of the leading causes of disease-induced deaths. Existing studies indicate that as urbanization increases, there is corresponding decrease in malaria prevalence. However, in malaria-endemic areas, the prevalence in some rural areas is sometimes lower than in some peri-urban and urban areas. Therefore, the relationship between the degree of urbanization, the impact of living in urban areas, and the prevalence of malaria remains unclear. This study explores this association in Ghana, using epidemiological data at the district level (2015-2018) and data on health, hygiene, and education. We applied a multilevel model and time series decomposition to understand the epidemiological pattern of malaria in Ghana. Then we classified the districts of Ghana into rural, peri-urban, and urban areas using administratively defined urbanization, total built areas, and built intensity. We converted the prevalence time series into cross-sectional data for each district by extracting features from the data. To predict the determinant most impacting according to the degree of urbanization, we used a cluster-specific random forest. We find that prevalence is impacted by seasonality, but the trend of the seasonal signature is not noticeable in urban and peri-urban areas. While urban districts have a slightly lower prevalence, there are still pockets with higher rates within these regions. These areas of high prevalence are linked to proximity to water bodies and waterways, but the rise in these same variables is not associated with the increase of prevalence in peri-urban areas. The increase in nightlight reflectance in rural areas is associated with an increased prevalence. We conclude that urbanization is not the main factor driving the decline in malaria. However, the data indicate that understanding and managing malaria prevalence in urbanization will necessitate a focus on these contextual factors. Finally, we design an interactive tool, 'malDecision' that allows data-supported decision-making., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Savi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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35. Exploring existing malaria services and the feasibility of implementing community engagement approaches amongst conflict-affected communities in Cameroon: a qualitative study.
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Ebob Besem E O M, Chestnutt EG, Donovan L, Stratil AS, Counihan H, Nkfusai CN, Hawkings H, Homolova B, Maxwell K, Baker K, Zoungrana Y, Tanue EA, Ayuk G, Modjenpa NB, Metuge A, Nganmou I, Achu D, Wanji S, Berryman E, and Omam LA
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- Cameroon, Humans, Community Health Workers statistics & numerical data, Focus Groups, Community Participation statistics & numerical data, Male, Female, Adult, Malaria prevention & control, Qualitative Research, Health Services Accessibility statistics & numerical data
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Background: Cameroon is one of the countries with the highest burden of malaria. Since 2018, there has been an ongoing conflict in the country, which has reduced access to healthcare for populations in affected regions, and little is known about the impact on access to malaria services. The objective of this study was to understand the current situation regarding access to malaria services in Cameroon to inform the design of interventions to remove barriers and encourage the use of available services., Methods: A qualitative research study was carried out to understand the barriers preventing communities accessing care, the uptake of community health worker (CHW) services, and to gather perceptions on community engagement approaches, to assess whether these could be an appropriate mechanism to encourage uptake of community health worker (CHW) services. Twenty-nine focus group discussions and 11 in-depth interviews were carried out between May and July 2021 in two regions of Cameroon, Southwest and Littoral. Focus group discussions were held with CHWs and community members and semi-structured, in-depth interviews were conducted with key stakeholders including regional government staff, council staff, community leaders and community-based organisations. The data were analysed thematically; open, descriptive coding was combined with exploration of pre-determined investigative areas., Results: The study confirmed that access to healthcare has become increasingly challenging in conflict-affected areas. Although the Ministry of Health are providing CHWs to improve access, several barriers remain that limit uptake of these services including awareness, availability, cost, trust in competency, and supply of testing and treatment. This study found that communities were supportive of community engagement approaches, particularly the community dialogue approach., Conclusion: Communities in conflict-affected regions of Cameroon continue to have limited access to healthcare services, in part due to poor use of CHW services provided. Community engagement approaches can be an effective way to improve the awareness and use of CHWs. However, these approaches alone will not be sufficient to resolve all the challenges faced by conflict-affected communities when accessing health and malaria services. Additional interventions are needed to increase the availability of CHWs, improve the supply of diagnostic tests and treatments and to reduce the cost of treatment for all., (© 2024. The Author(s).)
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- 2024
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36. Distribution and dynamics of Anopheles gambiae s.l. larval habitats in three Senegalese cities with high urban malaria incidence.
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Ndiaye F, Diop A, Chabi J, Sturm-Ramirez K, Senghor M, Diouf EH, Samb B, Diedhiou SM, Thiaw O, Zohdy S, Dotson E, Sene D, Diouf MB, Koscelnik V, Gerberg L, Bangoura A, Clark T, Faye O, Dia I, Konate L, and Niang EHA
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- Animals, Senegal epidemiology, Incidence, Humans, Anopheles parasitology, Ecosystem, Malaria epidemiology, Malaria transmission, Larva, Mosquito Vectors parasitology, Seasons, Cities
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Urban malaria has become a challenge for most African countries due to urbanization, with increasing population sizes, overcrowding, and movement into cities from rural localities. The rapid expansion of cities with inappropriate water drainage systems, abundance of water storage habitats, coupled with recurrent flooding represents a concern for water-associated vector borne diseases, including malaria. This situation could threaten progress made towards malaria elimination in sub-Saharan countries, including Senegal, where urban malaria has presented as a threat to national elimination gains. To assess drivers of urban malaria in Senegal, a 5-month study was carried out from August to December 2019 in three major urban areas and hotspots for malaria incidence (Diourbel, Touba, and Kaolack) including the rainy season (August-October) and partly dry season (November-December). The aim was to characterize malaria vector larval habitats, vector dynamics across both seasons, and to identify the primary eco- environmental entomological factors contributing to observed urban malaria transmission. A total of 145 Anopheles larval habitats were found, mapped, and monitored monthly. This included 32 in Diourbel, 83 in Touba, and 30 in Kaolack. The number of larval habitats fluctuated seasonally, with a decrease during the dry season. In Diourbel, 22 of the 32 monitored larval habitats (68.75%) were dried out by December and considered temporary, while the remaining 10 (31.25%) were classified as permanent. In the city of Touba 28 (33.73%) were temporary habitats, and of those 57%, 71% and 100% dried up respectively by October, November, and December. However, 55 (66.27%) habitats were permanent water storage basins which persisted throughout the study. In Kaolack, 12 (40%) permanent and 18 (60%) temporary Anopheles larval habitats were found and monitored during the study. Three malaria vectors (An. arabiensis, An. pharoensis and An. funestus s.l.) were found across the surveyed larval habitats, and An. arabiensis was found in all three cities and was the only species found in the city of Diourbel, while An. arabiensis, An. pharoensis, and An. funestus s.l. were detected in the cities of Touba and Kaolack. The spatiotemporal observations of immature malaria vectors in Senegal provide evidence of permanent productive malaria vector larval habitats year-round in three major urban centers in Senegal, which may be driving high urban malaria incidence. This study aimed to assess the presence and type of anopheline larvae habitats in urban areas. The preliminary data will better inform subsequent detailed additional studies and seasonally appropriate, cost-effective, and sustainable larval source management (LSM) strategies by the National Malaria Control Programme (NMCP)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
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- 2024
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37. Therapeutic efficacy and tolerability of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Niger, 2020.
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Laminou IM, Issa I, Adehossi E, Maman K, Jackou H, Coulibaly E, Tohon ZB, Ahmed J, Sanoussi E, and Koko D
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- Child, Preschool, Humans, Niger, Child, Infant, Adolescent, Male, Female, Drug Resistance genetics, Artemether, Lumefantrine Drug Combination therapeutic use, Malaria, Falciparum drug therapy, Antimalarials therapeutic use, Antimalarials adverse effects, Plasmodium falciparum drug effects, Plasmodium falciparum genetics
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Background: Monitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapy (ACT) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether-lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya, in Niger., Methods: A multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1000-200,000 asexual parasites/μL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan-Meier curve assessed parasite clearance., Results: A total of 255 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4-101.0%), 92.2% (85.0-98.5%) and 97.1% (93.1-101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance., Conclusion: The study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations. Trial registration NCT05070520, October 7, 2021., (© 2024. The Author(s).)
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- 2024
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38. A qualitative look at bed net access and use in Burkina Faso, Mozambique, Nigeria, and Rwanda following piloted distributions of dual-active ingredient insecticide-treated nets.
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Shannon J, Kagone M, Candrinho B, Otikwu S, Ingabire C, Gansane A, Pooda S, Aboubacar F, Ouattara F, Savaio B, Joanguete C, Sixpence L, Koenker H, Uhomoibhi P, Okoko OO, Ali O, Babarinde D, Ogundairo J, Lemah AS, Mbituyumuremyi A, Singirankabo JH, Kawakyu N, Guglielmo F, Fornadel C, Arnett K, Wagman J, Gogue C, Tynuv K, Digre P, Mwesigwa J, and Robertson M
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- Nigeria, Burkina Faso, Humans, Mozambique, Female, Rwanda, Male, Adult, Middle Aged, Young Adult, Focus Groups, Insecticide-Treated Bednets statistics & numerical data, Malaria prevention & control, Mosquito Control methods, Mosquito Control statistics & numerical data
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Background: Universal coverage with insecticide-treated nets (ITNs) is important for malaria control and elimination. The emergence and intensification of insecticide resistance threatens progress made through the deployment of these interventions and has required the development of newer, more expensive ITN types. Understanding malaria prevention behaviour, including barriers and facilitators to net access and use, can support effective decision-making for the promotion and distribution of ITNs., Methods: In-depth interviews and focus group discussions were conducted in 3 to 4 villages per district, in 13 districts across Burkina Faso, Mozambique, Nigeria and Rwanda from 2019 to 2022. Interviews were conducted in the local language, translated and transcribed in English, French or Portuguese. Transcripts were coded and analysed using Nvivo and ATLAS.ti., Results: ITNs were obtained from mass distribution campaigns, antenatal care and immunization visits, and purchased on the private market in some locations. While there were divergent perspectives in whether the number of distributed nets were adequate, participants consistently expressed concerns of bias, discrimination, and a lack of transparency with the distribution process. ITNs were frequently used alongside other malaria prevention methods. The primary motivation for use was malaria prevention. While some participants reported using nets nightly throughout the year, other participants reported seasonal use, both due to the perceived higher density of mosquitoes and discomfort of sleeping under a net in the increased heat. Other barriers to consistent net use included activities that take place away from the home, sleeping patterns and arrangements, and sensitivity to the insecticides on the nets., Conclusions: ITNs remain an important malaria control intervention. To ensure adequate and increased net access, distribution campaigns should consider family structures, available sleeping spaces, and other bed sharing preferences when identifying the number of nets needed for distribution. In addition, campaigns should allow for multiple options for net distribution points and timing to accommodate households remote to health services. Continuous distribution channels and complimentary distribution through the private sector could help fill gaps in coverage. Solutions are needed for outdoor malaria transmission, including alternative designs for ITNs, and improving access to complementary personal protective measures., (© 2024. The Author(s).)
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- 2024
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39. Identifying and characterizing high-risk populations in pilot malaria elimination districts in Madagascar: a mixed-methods study.
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Gebreegziabher E, Raoliarison A, Ramananjato A, Fanomezana A, Rafaliarisoa M, Ralisata S, Razafindrakoto J, Smith JL, Ahmed J, and Smith Gueye C
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- Madagascar epidemiology, Humans, Female, Male, Adult, Adolescent, Young Adult, Case-Control Studies, Child, Middle Aged, Risk Factors, Child, Preschool, Infant, Disease Eradication statistics & numerical data, Pilot Projects, Aged, Risk Assessment, Malaria prevention & control, Malaria epidemiology
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Background: In Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery., Methods: This mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case-control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case-control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders., Results: In Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation., Conclusions: The study results illustrate the value of in-depth assessments of risk behaviours, access to services and prevention tools, surveillance and prevention strategies, and the involvement of gatekeepers in shaping subnational tailoring to reach previously unreached populations and address residual transmission in elimination settings., (© 2024. The Author(s).)
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- 2024
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40. The Anopheles coluzzii range extends into Kenya: detection, insecticide resistance profiles and population genetic structure in relation to conspecific populations in West and Central Africa.
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Kamau L, Bennett KL, Ochomo E, Herren J, Agumba S, Otieno S, Omoke D, Matoke-Muhia D, Mburu D, Mwangangi J, Ramaita E, Juma EO, Mbogo C, Barasa S, and Miles A
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- Animals, Kenya, Genetics, Population, Africa, Western, Insecticides pharmacology, Africa, Central, Female, Anopheles genetics, Anopheles drug effects, Anopheles classification, Insecticide Resistance genetics, Mosquito Vectors genetics, Mosquito Vectors drug effects
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Background: Anopheles coluzzii is a primary vector of malaria found in West and Central Africa, but its presence has hitherto never been documented in Kenya. A thorough understanding of vector bionomics is important as it enables the implementation of targeted and effective vector control interventions. Malaria vector surveillance efforts in the country have tended to focus on historically known primary vectors. The current study sought to determine the taxonomic status of samples collected from five different malaria epidemiological zones in Kenya as well as describe the population genetic structure and insecticide resistance profiles in relation to other An. coluzzii populations., Methods: Mosquitoes were sampled as larvae from Busia, Kwale, Turkana, Kirinyaga and Kiambu counties, representing the range of malaria endemicities in Kenya, in 2019 and 2021 and emergent adults analysed using Whole Genome Sequencing (WGS) data processed in accordance with the Anopheles gambiae 1000 Genomes Project phase 3. Where available, historical samples from the same sites were included for WGS. Comparisons were made with An. coluzzii cohorts from West and Central Africa., Results: This study reports the detection of An. coluzzii for the first time in Kenya. The species was detected in Turkana County across all three time points from which samples were analyzed and its presence confirmed through taxonomic analysis. Additionally, there was a lack of strong population genetic differentiation between An. coluzzii from Kenya and those from the more northerly regions of West and Central Africa, suggesting they represent a connected extension to the known species range. Mutations associated with target-site resistance to DDT and pyrethroids and metabolic resistance to DDT were found at high frequencies up to 64%. The profile and frequencies of the variants observed were similar to An. coluzzii from West and Central Africa but the ace-1 mutation linked to organophosphate and carbamate resistance present in An. coluzzii from coastal West Africa was absent in Kenya., Conclusions: These findings emphasize the need for the incorporation of genomics in comprehensive and routine vector surveillance to inform on the range of malaria vector species, and their insecticide resistance status to inform the choice of effective vector control approaches., (© 2024. The Author(s).)
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- 2024
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41. Publisher Correction: Progress towards malaria elimination in the Greater Mekong Subregion: perspectives from the World Health Organization.
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Manzoni G, Try R, Guintran JO, Christiansen-Jucht C, Jacoby E, Sovannaroth S, Zhang Z, Banouvong V, Shortus MS, Reyburn R, Chanthavisouk C, Linn NYY, Thapa B, Khine SK, Sudathip P, Gopinath D, Thieu NQ, Ngon MS, Cong DT, Hui L, Kelley J, Valecha NNK, Bustos MD, Rasmussen C, and Tuseo L
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- 2024
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42. Malaria Species Positivity Rates Among Symptomatic Individuals Across Regions of Differing Transmission Intensities in Mainland Tanzania.
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Popkin-Hall ZR, Seth MD, Madebe RA, Budodo R, Bakari C, Francis F, Pereus D, Giesbrecht DJ, Mandara CI, Mbwambo D, Aaron S, Lusasi A, Lazaro S, Bailey JA, Juliano JJ, and Ishengoma DS
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- Humans, Tanzania epidemiology, Cross-Sectional Studies, Plasmodium malariae genetics, Malaria epidemiology, Malaria, Falciparum epidemiology
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Background: Recent data indicate that non-Plasmodium falciparum species may be more prevalent than thought in sub-Saharan Africa. Although Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax are less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized., Methods: We randomly selected 3284 of 12 845 samples collected from cross-sectional surveys in 100 health facilities across 10 regions of Mainland Tanzania and performed quantitative real-time PCR to determine presence and parasitemia of each malaria species., Results: P. falciparum was most prevalent, but P. malariae and P. ovale were found in all but 1 region, with high levels (>5%) of P. ovale in 7 regions. The highest P. malariae positivity rate was 4.5% in Mara and 8 regions had positivity rates ≥1%. We only detected 3 P. vivax infections, all in Kilimanjaro. While most nonfalciparum malaria-positive samples were coinfected with P. falciparum, 23.6% (n = 13 of 55) of P. malariae and 14.7% (n = 24 of 163) of P. ovale spp. were monoinfections., Conclusions: P. falciparum remains by far the largest threat, but our data indicate that malaria elimination efforts in Tanzania will require increased surveillance and improved understanding of the biology of nonfalciparum species., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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43. A formative cross-sectional study to assess caregiver's health-seeking behaviour and knowledge surrounding malaria, and understand the burden of malaria among children under-five in conflict-affected communities of Cameroon.
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Tanue EA, Omam LA, Ayuk GT, Noukeme BM, Metuge A, Nganmou I, Ebob MB, Donovan L, Stratil AS, Counihan H, Nkfusai CN, Hawkings H, Homolova B, Berryman E, Kolawole M, Zoungrana Y, Achu D, Wanji S, and Omam EN
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- Adult, Child, Humans, Cross-Sectional Studies, Cameroon epidemiology, Health Knowledge, Attitudes, Practice, Patient Acceptance of Health Care, Caregivers, Malaria epidemiology, Malaria prevention & control, Malaria diagnosis
- Abstract
Background: Malaria remains a major global health problem often worsened by political instability and armed conflict. The purpose of the study was to explore community knowledge, attitudes and practices on malaria prevention, and to understand the burden of malaria and health-seeking behaviours of caregivers of children under-five in conflict-affected communities of the South West and Littoral Regions of Cameroon., Methods: A cross-sectional survey involving internally displaced persons (IDPS), host population, and their children under-five was conducted across 80 communities. The survey was conducted from May to June 2021. Participants were interviewed using a structured questionnaire. Malaria prevalence for children under-five was determined using rapid diagnostic tests (RDT) on blood samples. Association between variables and displacement status was measured using chi square test and multivariate logistic regression model was fitted to identify factors associated with adequate knowledge on malaria prevention., Results: A total of 2386 adults participated in the study and 1543 RDTs were conducted for children under-five. Adequate levels of knowledge and attitudes on malaria prevention was recorded among 1258 (52.9%) of the participants, with very strong evidence to suggest the level to be higher among the host (59.5%) compared to the IDPs (49.5%) and returnees (39.7%) (p < 0.001). Good practices towards malaria prevention was 43.3%, with very strong evidence indicating lower levels among IDPs (42.8%) and returnees (28.5%) compared to the host (49.4%) (p < 0.001). Malaria prevalence for children under-five was 54.0% and adequate health-seeking for suspected episodes of malaria was 53.0%, without any difference among IDPs (51.78%) and returnees (48.7%) compared to host populations (55.4%) (p = 0.154). Multivariate logistic regression model showed that there was quite strong evidence to suggest primary and secondary levels of education have higher odds of having correct knowledge of malaria prevention (adjusted odds ratio (AOR) 1.71, 95% confidence interval (CI): 1.11-2.64, p = 0.015 and AOR 1.80, 95% CI 1.15-2.82, p = 0.010 respectively). There was very strong evidence to suggest that owning a radio or a television was associated with greater odds of having a higher knowledge on malaria prevention (AOR 1.49, 95% CI 1.233-1.81, p = 0.000 and AOR 1.47, 95% CI 1.18-1.84, p = 0.001)., Conclusion: Over half of the population have correct knowledge and attitudes towards malaria prevention but gaps in complete knowledge remained. Some of the caregivers know the correct malaria preventive practices coupled with largely unsatisfactory treatment approaches and reflected by the high prevalence of malaria among their children. In order to effectively treat malaria, innovative strategies should target community participation., (© 2024. The Author(s).)
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- 2024
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44. Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021.
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Rogier E, Battle N, Bakari C, Seth MD, Nace D, Herman C, Barakoti A, Madebe RA, Mandara CI, Lyimo BM, Giesbrecht DJ, Popkin-Hall ZR, Francis F, Mbwambo D, Garimo I, Aaron S, Lusasi A, Molteni F, Njau R, Cunningham JA, Lazaro S, Mohamed A, Juliano JJ, Bailey JA, Udhayakumar V, and Ishengoma DS
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- Humans, Plasmodium falciparum genetics, Protozoan Proteins genetics, Gene Deletion, Tanzania epidemiology, Diagnostic Tests, Routine methods, Antigens, Protozoan genetics, Health Facilities, DNA, Malaria, Falciparum diagnosis, Malaria, Falciparum epidemiology, Malaria, Falciparum genetics, Blood Group Antigens
- Abstract
Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7863 persons of all ages enrolled and providing RDT result and blood sample, 3777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n = 9) or only pfhrp3 (n = 6). No dual pfhrp2/3 deleted parasites were observed. This survey found that parasites with these gene deletions are rare in Tanzania, and estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania., (© 2024. The Author(s).)
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- 2024
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45. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018.
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Ngasala B, Chiduo MG, Bushukatale S, Mmbando BP, Makene T, Kamugisha E, Ahmed M, Mandara CI, Francis F, Mahende MK, Kavishe RA, Muro F, Ishengoma DS, Mandike R, Molteni F, Chacky F, Kitojo C, Greer G, Bishanga D, Chadewa J, Njau R, Warsame M, Kabula B, Nyinondi SS, Reaves E, and Mohamed A
- Subjects
- Child, Humans, Artemether, Lumefantrine Drug Combination adverse effects, Tanzania, Reinfection chemically induced, Reinfection drug therapy, Artemether therapeutic use, Amodiaquine therapeutic use, Fever drug therapy, Drug Combinations, Ethanolamines adverse effects, Plasmodium falciparum, Antimalarials adverse effects, Artemisinins adverse effects, Malaria, Falciparum drug therapy, Malaria, Falciparum prevention & control, Malaria drug therapy
- 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 °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., (© 2024. The Author(s).)
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- 2024
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46. Prevalence of non-falciparum malaria infections among asymptomatic individuals in four regions of Mainland Tanzania.
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Popkin-Hall ZR, Seth MD, Madebe RA, Budodo R, Bakari C, Francis F, Pereus D, Giesbrecht DJ, Mandara CI, Mbwambo D, Aaron S, Lusasi A, Lazaro S, Bailey JA, Juliano JJ, Gutman JR, and Ishengoma DS
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- Humans, Asymptomatic Infections epidemiology, Cross-Sectional Studies, Plasmodium falciparum, Plasmodium malariae, Prevalence, Tanzania epidemiology, Malaria epidemiology, Malaria, Falciparum epidemiology, Malaria, Vivax epidemiology
- Abstract
Background: Recent studies point to the need to incorporate the detection of non-falciparum species into malaria surveillance activities in sub-Saharan Africa, where 95% of the world's malaria cases occur. Although malaria caused by infection with Plasmodium falciparum is typically more severe than malaria caused by the non-falciparum Plasmodium species P. malariae, P. ovale spp. and P. vivax, the latter may be more challenging to diagnose, treat, control and ultimately eliminate. The prevalence of non-falciparum species throughout sub-Saharan Africa is poorly defined. Tanzania has geographical heterogeneity in transmission levels but an overall high malaria burden., Methods: To estimate the prevalence of malaria species in Mainland Tanzania, we randomly selected 1428 samples from 6005 asymptomatic isolates collected in previous cross-sectional community surveys across four regions and analyzed these by quantitative PCR to detect and identify the Plasmodium species., Results: Plasmodium falciparum was the most prevalent species in all samples, with P. malariae and P. ovale spp. detected at a lower prevalence (< 5%) in all four regions; P. vivax was not detected in any sample., Conclusions: The results of this study indicate that malaria elimination efforts in Tanzania will need to account for and enhance surveillance of these non-falciparum species., (© 2024. The Author(s).)
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- 2024
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47. Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017.
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Ngasala B, Chacky F, Mohamed A, Molteni F, Nyinondi S, Kabula B, Mkali H, Thwai K, Popkin-Hall ZR, Mitchell C, Parr JB, Juliano JJ, and Lin JT
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- Child, Female, Humans, Male, Gene Deletion, Polymerase Chain Reaction methods, Prevalence, Rapid Diagnostic Tests, Schools, Sensitivity and Specificity, Tanzania epidemiology, Antigens, Protozoan genetics, Malaria, Falciparum diagnosis, Malaria, Falciparum epidemiology, Plasmodium falciparum genetics, Plasmodium falciparum isolation & purification, Protozoan Proteins genetics
- Abstract
As part of malaria nationwide monitoring and evaluation initiatives, there is an increasing trend of incorporating malaria rapid diagnostic tests (mRDTs) in surveys conducted within primary schools to detect malaria parasites. However, mRDTs based on the detection of histidine-rich protein 2 (HRP2) are known to yield false-positive results due to persistent antigenemia, and false-negative results may result from low parasitemia or Plasmodium falciparum hrp2/3 gene deletion. We evaluated diagnostic performance of an HRP2 and pan-parasite lactate dehydrogenase (HRP2/pLDH) mRDT against polymerase chain reaction (PCR) for detection of P. falciparum among 17,051 primary school-age children from eight regions of Tanzania in 2017. According to PCR, the prevalence of P. falciparum was 19.2% (95% CI: 18.6-19.8). Using PCR as reference, the sensitivity and specificity of mRDT was 76.2% (95% CI: 74.7-77.7) and 93.9% (95% CI: 93.5-94.3), respectively. Test agreement was lowest in low transmission areas, where true-positive mRDTs were outnumbered by false-negatives due to low parasitemia. Discordant samples (mRDT-negative but PCR-positive) were screened for pfhrp2/3 deletion by real-time PCR. Among those with a parasite density sufficient for analysis, pfhrp2 deletion was confirmed in 60 samples, whereas pfhrp3 deletion was confirmed in two samples; one sample had both pfhrp2 and pfhrp3 deletions. The majority of samples with gene deletions were detected in the high-transmission Kagera region. Compared with mRDTs, PCR and other molecular methods offer increased sensitivity and are not affected by pfhrp2/3 deletions, making them a useful supplement to mRDTs in schools and other epidemiological surveys.
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- 2024
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48. Food insecurity and associated health and social determinants among older adults in Ghana: Analysis of the WHO's study on global AGEing and adult health (SAGE), 2014-2015.
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Tetteh J, Ekem-Ferguson G, Malm K, Yawson OA, Otchi E, Swaray SM, Yao Ntumy M, and Yawson AE
- Abstract
This study was conducted to assess the prevalence and factors associated with Food Insecurity (FI) and further quantify its association with unmet need for health services and health-related outcomes among older adults aged 50 years and above in Ghana. The Ghana Study on Global AGEing and Adult Health was used. Body Mass Index (BMI), depressive episodes, functional difficulties (FD), low Quality of Life (QoL), memory decline, and Unmet Needs of Health Services (UNHS) are the the study outcomes. Ordinary Least Square, and Poisson regression analysis modified with Mahalanobis distance matching within propensity score caliper weights were employed. Stata 16.1 was used to perform analysis and a p-value < 0.05 was deemed significant. The prevalence of FI among older adults aged 50 years or older in Ghana was approximately 28 %(95 %CI = 24.5-31.7) and was strongly associated with lower educational attainment and social support. The prevalence ratio of depression, FD, low QoL and UNHS among older adults who experienced FI were; 3.43(95 %CI = 2.25-5.21), 1.18(95 %CI = 1.12-1.23), 2.01(95 %CI = 1.54-2.62), and 1.46(95 %CI = 1.01-2.11). Memory significantly decreased by 85 percentage points% among food insecure older adults [aβ(95 %CI) = -0.85(-1.62--0.07)]. Older adults with relatively higher educational attainment and social support are less likely to suffer FI and associated limited health and poor social well-being. In the national quest to achieve SDG 2, these health and social determinants of FI among older adults should be considered in the implementation of the national ageing policy to improve the health and well-being of older adults in Ghana., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)
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- 2024
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49. Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania.
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Ishengoma DS, Mandara CI, Madebe RA, Warsame M, Ngasala B, Kabanywanyi AM, Mahende MK, Kamugisha E, Kavishe RA, Muro F, Mandike R, Mkude S, Chacky F, Njau R, Martin T, Mohamed A, Bailey JA, and Fola AA
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- Humans, Protozoan Proteins metabolism, Genetic Variation, Tanzania, Merozoite Surface Protein 1 genetics, Plasmodium falciparum genetics, Plasmodium falciparum metabolism, Genotype, Microsatellite Repeats, Antigens, Protozoan genetics, Antimalarials pharmacology, Antimalarials therapeutic use, Malaria, Falciparum parasitology
- Abstract
Background: Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania., Methods: Plasmodium falciparum samples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-α, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites., Results: Overall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for ≥ 50.0% of the markers), and > 50.0% of the samples (range = 47.6-59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (R
S = 7.48, range = 7.27-8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (He = 0.83, range = 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (FST ) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-α was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic., Conclusion: Microsatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-α, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-α alone or with any of the other three markers could be adopted for use in TES in Tanzania., (© 2024. The Author(s).)- Published
- 2024
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50. Molecular and entomological surveillance of malaria vectors in urban and rural communities of Benguela Province, Angola.
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Alves G, Troco AD, Seixas G, Pabst R, Francisco A, Pedro C, Garcia L, Martins JF, and Lopes S
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- Animals, Female, Rural Population, Angola, Mosquito Vectors genetics, Malaria, Anopheles genetics, Malaria, Falciparum
- Abstract
Background: Malaria is a major public health problem in Angola, with Anopheles gambiae sensu lato (s.l.) and An. funestus s.l. being the primary vectors. This study aimed to clarify the information gaps concerning local Anopheles mosquito populations. Our objectives were to assess their abundance, geographical dispersion, and blood-feeding patterns. We also investigated their insecticide resistance. Molecular methods were used to identify sibling species, determine the origin of blood meals, measure Plasmodium falciparum infection rates, and detect the presence of knockdown resistance (kdr) mutations., Methods: Adult mosquitoes were collected indoors using CDC light traps from nine randomly selected households at two sentinel sites with distinct ecological characteristics. The samples were collected from 1 February to 30 June 2022. Anopheles mosquitoes were morphologically identified and subjected to molecular identification. Unfed Anopheles females were tested for the presence of P. falciparum DNA in head and thorax, and engorged females were screened for the source of the blood meals. Additionally, members of An. gambiae complex were genotyped for the presence of the L1014F and L1014S kdr mutations., Results: In total, 2226 adult mosquitoes were collected, including 733 Anopheles females. Molecular identification revealed the presence of Anopheles coluzzii, An. gambiae senso stricto (s.s.), An. arabiensis, and An. funestus s.s. Notably, there was the first record of An. coluzzii/An. gambiae s.s. hybrid and An. vaneedeni in Benguela Province. Plasmodium falciparum infection rates for An. coluzzii at the urban sentinel site and An. funestus s.s. at the rural site were 23.1% and 5.7%, respectively. The L1014F kdr mutation was discovered in both resistant and susceptible An. coluzzii mosquitoes, while the L1014S mutation was detected in An. gambiae s.s. for the first time in Benguela Province. No kdr mutations were found in An. arabiensis., Conclusions: This study provides valuable insights into the molecular characteristics of malaria vectors from the province of Benguela, emphasising the need for continuous surveillance of local Anopheles populations regarding the establishment of both kdr mutations for tailoring vector control interventions., (© 2024. The Author(s).)
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- 2024
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