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-
1.
Institute of Medicine (US) Committee to Review the Department of Defense Global Emerging Infections Surveillance and Response System , 2001. Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review. Brachman PS , O’Maonaigh HC & Miller RN Washington, DC: The National Academies Press.
-
2.
Walter Reed Army Institute of Research (WRAIR) , 2023. Global Research Network. Available at: https://wrair.health.mil/Global-Research/. Accessed November 29, 2023.
-
3.
KEMRI , 2023. Kenya Medical Research Institute, KEMRI. Available at: https://www.kemri.go.ke/. Accessed November 29, 2023.
-
4.
Sifuna P et al., 2014. Health and demographic surveillance system profile: The Kombewa health and demographic surveillance system (Kombewa HDSS). Int J Epidemiol 43: 1097–1104.
-
5.
Jenkins R , Ongecha M , Othieno C , Ongeri L , Sifuna P , Omollo R , Leonard B , Ogutu B , 2020. Malaria, mental disorders and immunity; and their inter-relationships—A cross sectional study in a health and demographic surveillance site in Kenya. SSRN Electron J 39: 369–376.
-
6.
Otieno L et al., 2016. Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: A randomised, double-blind, controlled trial. Lancet Infect Dis 16: 1134–1144.
-
7.
RTS,S Clinical Trials Partnership , et al.2011. First results of phase 3 trial of rts,s/as01 malaria vaccine in African children. N Engl J Med 365: 1863–1875.
-
8.
Polhemus ME et al., 2009. Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area. PLoS One 4: e6465.
-
9.
Ogutu BR et al., 2009. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One 4: e4708.
-
10.
Otsyula N et al., 2013. Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142) administered intramuscularly with adjuvant system AS01. Malar J 12: 29.
-
11.
Li Q et al., 2014. Pharmacokinetic evaluation of intravenous artesunate in adults with uncomplicated falciparum malaria in Kenya: A phase II study. Malar J 13: 281.
-
12.
Abdulla S , Sagara I , 2009. Dispersible formulation of artemether/lumefantrine: Specifically developed for infants and young children. Malar J 8 (Suppl 1 ):S7.
-
13.
Dow GS , Liu J , Lin G , Hetzell B , Thieling S , McCarthy WF , Tang D , Smith B , 2015. Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries. Malar. J 14: 1–3.
-
14.
Chandra R , Ansah P , Sagara I , Sie A , Tiono AB , Djimde AA , Zhao Q , Robbins J , Penali LK , Ogutu B , 2015. Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: A randomized, open-label study. Malar J 14: 108.
-
15.
Held J et al., 2015. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: A phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study. Lancet Infect Dis 15: 1409–1419.
-
16.
Akala HM et al., 2021. Plasmodium interspecies interactions during a period of increasing prevalence of Plasmodium ovale in symptomatic individuals seeking treatment: An observational study. Lancet Microbe 2: e141–e150.
-
17.
Apinjoh TO , Ouattara A , Titanji VPK , Djimde A , Amambua-Ngwa A , 2019. Genetic diversity and drug resistance surveillance of Plasmodium falciparum for malaria elimination: Is there an ideal tool for resource-limited sub-Saharan Africa? Malar J 18: 217.
-
18.
Chebon LJ et al., 2016. Genetically determined response to artemisinin treatment inwestern kenyan Plasmodium falciparum parasites. PLoS One 11: e0162524.
-
19.
Wakoli DM et al., 2022. Impact of parasite genomic dynamics on the sensitivity of Plasmodium falciparum isolates to piperaquine and other antimalarial drugs. BMC Med 20: 448.
-
20.
Muiruri P et al., 2018. Selective sweeps and genetic lineages of Plasmodium falciparum multi-drug resistance (pfmdr1) gene in Kenya. Malar J 17: 398.
-
21.
Cheruiyot AC et al., 2016. Assessment of the worldwide antimalarial resistance network standardized procedure for in vitro malaria drug sensitivity testing using SYBR green assay for field samples with various initial parasitemia levels. Antimicrob Agents Chemother 60: 2417–2424.
-
22.
Andagalu B et al., 2022. Age-dependent antibody profiles to Plasmodium antigens are differentially associated with two artemisinin combination therapy outcomes in high transmission setting. Front Med 9: 991807.
-
23.
de Laurent ZR , Chebon LJ , Ingasia LA , Akala HM , Andagalu B , Ochola-Oyier LI , Kamau E , 2018. Polymorphisms in the K13 gene in Plasmodium falciparum from different malaria transmission areas of Kenya. Am J Trop Med Hyg 98: 1360–1366.
-
24.
Yeda R , Ingasia LA , Cheruiyot AC , Okudo C , Chebon LJ , Cheruiyot J , Akala HM , Kamau E , 2016. The genotypic and phenotypic stability of Plasmodium falciparum field isolates in continuous in vitro culture. PLoS One 11: e0143565.
-
25.
Wanjala CNL , Bergmann-Leitner E , Akala HM , Odhiambo G , Ogutu BR , Andagalu B , Kamau E , Ochiel D , 2020. The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya. Malar J 19: 168.
-
26.
Mogire RM , Akala HM , Macharia RW , Juma DW , Cheruiyot AC , Andagalu B , Brown ML , El-Shemy HA , Nyanjom SG , 2017. Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets. PLoS One 12: e0186364.
-
27.
Gupta Y et al., 2022. The multistage antimalarial compound calxinin perturbates P. falciparum Ca2+ homeostasis by targeting a unique ion channel. Pharmaceutics 14: 1371.
-
28.
Miller WA III , Teye J , Achieng AO , Mogire RM , Akala H , Ong’echa JM , Rathi B , Durvasula R , Kempaiah P , Kwofie SK , 2018. Antimalarials: Review of plasmepsins as drug targets and hiv protease inhibitors interactions. Curr Top Med Chem 18: 2022–2028.
-
29.
Ohrt C et al., 2007. Establishing a malaria diagnostics centre of excellence in Kisumu, Kenya. Malar J 6: 79.
-
30.
Dhorda M et al., 2020. Towards harmonization of microscopy methods for malaria clinical research studies. Malar J 19: 324.
-
31.
Prudhomme O’Meara W et al., 2006. Systematic comparison of two methods to measure parasite density from malaria blood smears. Parasitol Res 99: 500–504.
-
32.
Gómez-Hoyos R , Cardona-Arias JA , Gutiérrez LFH , Salas-Zapata W , Carmona-Fonseca J , 2022. Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010–2022. Rev Peru Med Exp Salud Publica 39: 302–311.
-
33.
Vásquez AM , Medina AC , Tobón-Castaño A , Posada M , Vélez GJ , Campillo A , González IJ , Ding X , 2018. Performance of a highly sensitive rapid diagnostic test (HS-RDT) for detecting malaria in peripheral and placental blood samples from pregnant women in Colombia. PLoS One 13: e0201769.
-
34.
Fallis A , 2013. Malaria Microscopy Quality Assurance Manual: Version 2. Available at: https://www.who.int/docs/default-source/documents/publications/gmp/malaria-microscopy-quality-assurance-manual.pdf. Accessed August 23, 2013.
-
35.
Wanja E et al., 2017. Evaluation of a laboratory quality assurance pilot programme for malaria diagnostics in low-transmission areas of Kenya, 2013. Malar J 16: 221.
-
36.
Withers MR et al., 2006. Safety and reactogenicity of an MSP-1 malaria vaccine candidate: A randomized phase Ib dose-escalation trial in Kenyan children. PLoS Clin Trials 1: e32.
-
37.
Waitumbi JN et al., 2009. Impact of RTS,S/AS02A and RTS,S/AS01B on genotypes of P. falciparum in adults participating in a malaria vaccine clinical trial. PLoS One 4: e7849.
-
38.
Waitumbi JN , Kifude CM , Hunja CW , Ogutu BR , 2018. Females of HbAS genotype have reduced concentration of the malaria protective deoxyhemoglobin S than males. PLoS One 13: e0203455.
-
39.
Waitumbi JN , Kifude CM , Withers MR , Polhemus ME , Heppner DG , Ogutu BR , 2007. Hb G-Philadelphia or Stanleyville II? When the phenotype and genotype do not agree. Eur J Haematol 79: 177–178.
-
40.
Kifude CM , Polhemus ME , Heppner DG , Withers MR , Ogutu BR , Waitumbi JN , 2007. Hb Kenya among luo adults and young children in malaria holoendemic Western Kenya: Screened by high performance liquid chromatography and confirmed by polymerase chain reaction. Hemoglobin 31: 401–408.
-
41.
Carter N , Pamba A , Duparc S , Waitumbi JN , 2011. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J 10: 1–14.
-
42.
Manabe YC et al., 2022. Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: A prospective, multicentre, cross-sectional diagnostic accuracy study. Lancet Infect Dis 22: 1356–1364.
-
43.
Premji ZG , 2009. Coartem: The journey to the clinic. Malar J 8 (Suppl 1 ):S3.
-
44.
Medicines for Malaria Venture , 2021. Coartem Dispersible Facts. Available at: https://www.mmv.org/access/products-projects/coartem-dispersible-artemether-lumefantrine/coartem-dispersible-facts#:∼:text=Coartem. Accessed August 1, 2021.
-
45.
RTS,S Clinical Trials Partnership , 2015. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: Final results of a phase 3, individually randomised, controlled trial. Lancet 386: 31–45.
-
46.
European Medicines Agency , 2015. First malaria vaccine receives positive scientific opinion from EMA. Pharm J 295, doi: 10.1211/PJ.2015.20069061.
-
47.
Balakrishnan VS , 2021. WHO recommends malaria vaccine for children. Lancet Infect Dis 21: 1634.
-
48.
Gavi , 2023. 18 Million Doses of First-Ever Malaria Vaccine Allocated to 12 African Countries for 2023–2025: Gavi, WHO and UNICEF. Available at: https://www.gavi.org/news/media-room/18-million-doses-first-ever-malaria-vaccine-allocated-12-african-countries-2023. Accessed August 1, 2023.
-
49.
WHO , 2022. World Malaria Report 2022 .Geneva, Switzerland: World Health Organization.
-
50.
Kagoro FM , Barnes KI , Marsh K , Ekapirat N , Mercado CEG , Sinha I , Humphreys G , Dhorda M , Guerin PJ , Maude RJ , 2022. Mapping genetic markers of artemisinin resistance in Plasmodium falciparum malaria in Asia: A systematic review and spatiotemporal analysis. Lancet Microbe 3: e184–e192.
-
51.
Schmedes SE et al., 2021. Plasmodium falciparum kelch 13 mutations, 9 countries in Africa, 2014–2018. Emerg Infect Dis 27: 1902.
-
52.
Uwimana A et al., 2020. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med 26: 1602–1608.
-
53.
Bergmann C et al., 2021. Increase in kelch 13 polymorphisms in Plasmodium falciparum, southern Rwanda. Emerg Infect Dis 27: 294.
-
54.
Uwimana A et al., 2021. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: An open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis 21: 1120–1128.
-
55.
Conrad MD et al., 2023. Evolution of partial resistance to artemisinins in malaria parasites in Uganda. N Engl J Med 389: 722–732.
-
56.
Juliano JJ et al., 2023. Country Wide Surveillance Reveals Prevalent artemisinin Partial Resistance Mutations with Evidence for Multiple Origins and Expansion of High Level Sulfadoxine Pyrimethamine Resistance Mutations in Northwest Tanzania. Available at: https://doi.org/10.1101/2023.11.07.23298207. Accessed April 5, 2024.
-
57.
Stokes BH , Ward KEFD , 2022. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med 4: 1385.
-
58.
Balikagala B et al., 2021. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med 385: 1163–1171.
-
59.
Fola AA et al., 2023. Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia. Nat Microbiol 8: 1911–1919.
-
60.
Mihreteab S , Anderson K , la Fuente IM , Sutherland CJ , Smith D , Cunningham J , Beshir KB , Cheng Q , 2023. The Spread of a Validated Molecular Marker of Artemisinin Partial Resistance pfkelch13 R622I and Association with pfhrp2/3 Deletions in Eritrea. Available at: https://doi.org/10.1101/2023.10.20.23297302. Accessed April 5, 2024.
-
61.
Maniga JN et al., 2023. Novel Plasmodium falciparum k13 gene polymorphisms from Kisii County, Kenya during an era of artemisinin-based combination therapy deployment. Malar J 22: 87.
-
62.
Spalding MD , Eyase FL , Akala HM , Bedno SA , Prigge ST , Coldren RL , Moss WJ , Waters NC , 2010. Increased prevalence of the pfdhfr/phdhps quintuple mutant and rapid emergence of pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya. Malar J 9: 338.
-
63.
Mbaisi A et al., 2004. Drug susceptibility and genetic evaluation of Plasmodium falciparum isolates obtained in four distinct geographical regions of Kenya. Antimicrob Agents Chemother 48: 3598–3601.
-
64.
Juma DW et al., 2014. Trends in drug resistance codons in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Kenyan parasites from 2008 to 2012. Malar J 13: 250.
-
65.
Juma DW , Muiruri P , Yuhas K , John-Stewart G , Ottichilo R , Waitumbi J , Singa B , Polyak C , Kamau E , 2018. The prevalence and antifolate drug resistance profiles of Plasmodium falciparum in study participants randomized to discontinue or continue cotrimoxazole prophylaxis. PLoS Negl Trop Dis 13: e0007223.
-
66.
Cheruiyot J et al., 2014. Polymorphisms in Pfmdr1, Pfcrt, and Pfnhe1 genes are associated with reduced in vitro activities of quinine in Plasmodium falciparum isolates from western Kenya. Antimicrob Agents Chemother 58: 3737–3743.
-
67.
Achieng AO et al., 2015. Temporal trends in prevalence of Plasmodium falciparum molecular markers selected for by artemether-lumefantrine treatment in pre-ACT and post-ACT parasites in western Kenya. Int J Parasitol Drugs Drug Resist 5: 92–99.
-
68.
Eyase FL et al., 2013. The role of Pfmdr1 and Pfcrt in changing chloroquine, amodiaquine, mefloquine and lumefantrine susceptibility in western-Kenya P. falciparum samples during 2008–2011. PLoS One 8: e64299.
-
69.
Kamau E et al., 2015. Case report of attenuated-responsiveness to Coartem® in western Kenya. Int J Med Pharm Case Reports 2: 5–9.
-
70.
Obare P et al., 2013. Misclassification of Plasmodium infections by conventional microscopy and the impact of remedial training on the proficiency of laboratory technicians in species identification. Malar J 12: 113.
-
71.
Odhiambo F et al., 2017. Factors associated with malaria microscopy diagnostic performance following a pilot quality-assurance programme in health facilities in malaria low-transmission areas of Kenya, 2014. Malar J 16: 371.
-
72.
RTS,S Clinical Trials Partnership , 2012. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med 367: 2284–2295.
-
73.
White MT et al., 2015. Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: Secondary analysis of data from a phase 3 randomised controlled trial. Lancet Infect Dis 15: 1450–1458.
-
74.
Kamau E , Alemayehu S , Feghali KC , Juma DW , Blackstone GM , Marion WR , Obare P , Ogutu B , Ockenhouse CF , 2014. Sample-ready multiplex qPCR assay for detection of malaria. Malar J 13: 158.
-
75.
Ohrt C , O’Meara WP , Remich S , McEvoy P , Ogutu B , Mtalib R , Odera JS , 2008. Pilot assessment of the sensitivity of the malaria thin film. Malar J 7: 22.
-
76.
Morang’A C , Ayieko C , Awinda G , Achilla R , Moseti C , Ogutu B , Waitumbi J , Wanja E , 2018. Stabilization of RDT target antigens present in dried Plasmodium falciparum-infected samples for validating malaria rapid diagnostic tests at the point of care. Malar J 17: 10.
-
77.
Das D et al., 2022. Field evaluation of the diagnostic performance of EasyScan GO: A digital malaria microscopy device based on machine-learning. Malar J 21: 122.
-
78.
Horning MP et al., 2021. Performance of a fully‐automated system on a WHO malaria microscopy evaluation slide set. Malar J 20: 110.
-
79.
Wanja EW , Kuya N , Moranga C , Hickman M , Johnson JD , Moseti C , Anova L , Ogutu B , Ohrt C , 2016. Field evaluation of diagnostic performance of malaria rapid diagnostic tests in western Kenya. Malar J 15: 456.
-
80.
Stoute JA , Odindo AO , Owuor BO , Mibei EK , Opollo MO , Waitumbi JN , 2003. Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. J Infect Dis 187: 522–525.
-
81.
Korir JC , Nyakoe NK , Awinda G , Waitumbi JN , 2014. Complement activation by merozoite antigens of Plasmodium falciparum. PLoS One 9: e105093.
-
82.
Mutai BK , Waitumbi JN , 2010. Apoptosis stalks Plasmodium falciparum maintained in continuous culture condition. Malar J 9 (Suppl 3 ):S6.
-
83.
Bashir IM , Otsyula N , Awinda G , Spring M , Schneider P , Waitumbi JN , 2013. Comparison of PfHRP-2/pLDH ELISA, qPCR and microscopy for the detection of Plasmodium events and prediction of sick visits during a malaria vaccine study. PLoS One 8: e56828.
-
84.
Nyataya J , Waitumbi J , Mobegi VA , Noreddin A , El Zowalaty ME , 2020. Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions and their implications in malaria control. Diseases 8: 15.
-
85.
Andika B , Mobegi V , Gathii K , Nyataya J , Maina N , Awinda G , Mutai B , Waitumbi J , 2023. Plasmodium falciparum population structure inferred by msp1 amplicon sequencing of parasites collected from febrile patients in Kenya. Malar J 22: 263.
-
86.
Muthanje EM , Kimita G , Nyataya J , Njue W , Mulili C , Mugweru J , Mutai B , Kituyi SN , Waitumbi J , 2022. March 2019 dengue fever outbreak at the Kenyan south coast involving dengue virus serotype 3, genotypes III and V. PLOS Glob Public Health 2: e0000122.
-
87.
Nyataya J , Maraka M , Lemtudo A , Masakhwe C , Mutai B , Njaanake K , Estambale BB , Nyakoe N , Siangla J , Waitumbi JN , 2020. Serological evidence of yersiniosis, tick-borne encephalitis, West Nile, hepatitis E, Crimean-Congo hemorrhagic fever, Lyme borreliosis, and brucellosis in febrile patients presenting at diverse hospitals in Kenya. Vector Borne Zoonotic Dis 20: 348–357.
-
88.
Gathii K , Nyataya JN , Mutai BK , Awinda G , Waitumbi JN , 2018. Complete coding sequences of dengue virus type 2 strains from febrile patients seen in Malindi District Hospital, Kenya, during the 2017 dengue fever outbreak. Genome Announc 6: e00076-18.
-
89.
Davis LL , Broome ME , Cox RP , 2002. Maximizing retention in community-based clinical trials. J Nurs Scholarsh 34: 47–53.
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The Walter Reed Project, Kisumu Field Station: Impact of Research on Malaria Policy, Management, and Prevention
Peter M. Sifuna
Peter M. Sifuna
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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Michal Mbinji
Michal Mbinji
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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Tina O. Lucas
Tina O. Lucas
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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Irene Onyango
Irene Onyango
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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Hoseah M. Akala
Hoseah M. Akala
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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John N. Waitumbi
John N. Waitumbi
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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Bernhards R. Ogutu
Bernhards R. Ogutu
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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Jack N. Hutter
Jack N. Hutter
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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Walter Otieno
Walter Otieno
Kenya Medical Research Institute, Kisumu, Kenya;
U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya
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ABSTRACT.
The Walter Reed Project is a collaboration between the Walter Reed Army Institute of Research of the United States Department of Defense and the Kenya Medical Research Institute. The Kisumu field station, comprising four campuses, has until recently been devoted primarily to research on malaria countermeasures. The Kombewa Clinical Research Center is dedicated to conducting regulated clinical trials of therapeutic and vaccine candidates in development. The center’s robust population-based surveillance platform, along with an active community engagement strategy, guarantees consistent recruitment and retention of participants in clinical trials. The Malaria Diagnostic Center, backed by WHO-certified microscopists and a large malaria blood film collection, champions high-quality malaria diagnosis and strict quality assurance through standardized microscopy trainings. The Malaria Drug Resistance Laboratory leverages cutting-edge technology such as real-time Polymerase Chain Reaction (qPCR) to conduct comprehensive research on resistance markers and obtain information on drug efficacy. The laboratory has been working on validating artemisinin resistance markers and improving tracking methods for current and future antimalarial compounds. Finally, the Basic Science Laboratory employs advanced genomic technology to examine endpoints such as immunogenicity and genomic fingerprinting for candidate drugs and vaccine efficacy. Herein, we examine the site’s significant contributions to malaria policy, management, and prevention practices in Kenya and around the world.
Author Notes
Disclosures: Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the Department of the Army or the Department of Defense.
Authors’ addresses: Peter M. Sifuna, Michal Mbinji, Tina O. Lucas, Irene Onyango, Hoseah M. Akala, John N. Waitumbi, Bernhards R. Ogutu and Walter Otieno, Kenya Medical Research Institute, Kisumu, Kenya and U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya, E-mail: peter.sifuna@usamru-k.org, Michal.Ohaga@usamru-k.org, lucas.tina0818@gmail.com, Irene.Onyango@usamru-k.org, Hosea.Akala@usamru-k.org, John.Waitumbi@usamru-k.org, ogutu6@gmail.com, Walter.Otieno@usamru-k.org. Jack N. Hutter, U.S. Army Medical Research Directorate—Africa, Kisumu, Kenya, E-mail: jakofclubs@gmail.com.
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-
1.
Institute of Medicine (US) Committee to Review the Department of Defense Global Emerging Infections Surveillance and Response System , 2001. Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System: A Program Review. Brachman PS , O’Maonaigh HC & Miller RN Washington, DC: The National Academies Press.
-
2.
Walter Reed Army Institute of Research (WRAIR) , 2023. Global Research Network. Available at: https://wrair.health.mil/Global-Research/. Accessed November 29, 2023.
-
3.
KEMRI , 2023. Kenya Medical Research Institute, KEMRI. Available at: https://www.kemri.go.ke/. Accessed November 29, 2023.
-
4.
Sifuna P et al., 2014. Health and demographic surveillance system profile: The Kombewa health and demographic surveillance system (Kombewa HDSS). Int J Epidemiol 43: 1097–1104.
-
5.
Jenkins R , Ongecha M , Othieno C , Ongeri L , Sifuna P , Omollo R , Leonard B , Ogutu B , 2020. Malaria, mental disorders and immunity; and their inter-relationships—A cross sectional study in a health and demographic surveillance site in Kenya. SSRN Electron J 39: 369–376.
-
6.
Otieno L et al., 2016. Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: A randomised, double-blind, controlled trial. Lancet Infect Dis 16: 1134–1144.
-
7.
RTS,S Clinical Trials Partnership , et al.2011. First results of phase 3 trial of rts,s/as01 malaria vaccine in African children. N Engl J Med 365: 1863–1875.
-
8.
Polhemus ME et al., 2009. Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area. PLoS One 4: e6465.
-
9.
Ogutu BR et al., 2009. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One 4: e4708.
-
10.
Otsyula N et al., 2013. Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142) administered intramuscularly with adjuvant system AS01. Malar J 12: 29.
-
11.
Li Q et al., 2014. Pharmacokinetic evaluation of intravenous artesunate in adults with uncomplicated falciparum malaria in Kenya: A phase II study. Malar J 13: 281.
-
12.
Abdulla S , Sagara I , 2009. Dispersible formulation of artemether/lumefantrine: Specifically developed for infants and young children. Malar J 8 (Suppl 1 ):S7.
-
13.
Dow GS , Liu J , Lin G , Hetzell B , Thieling S , McCarthy WF , Tang D , Smith B , 2015. Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries. Malar. J 14: 1–3.
-
14.
Chandra R , Ansah P , Sagara I , Sie A , Tiono AB , Djimde AA , Zhao Q , Robbins J , Penali LK , Ogutu B , 2015. Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: A randomized, open-label study. Malar J 14: 108.
-
15.
Held J et al., 2015. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: A phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study. Lancet Infect Dis 15: 1409–1419.
-
16.
Akala HM et al., 2021. Plasmodium interspecies interactions during a period of increasing prevalence of Plasmodium ovale in symptomatic individuals seeking treatment: An observational study. Lancet Microbe 2: e141–e150.
-
17.
Apinjoh TO , Ouattara A , Titanji VPK , Djimde A , Amambua-Ngwa A , 2019. Genetic diversity and drug resistance surveillance of Plasmodium falciparum for malaria elimination: Is there an ideal tool for resource-limited sub-Saharan Africa? Malar J 18: 217.
-
18.
Chebon LJ et al., 2016. Genetically determined response to artemisinin treatment inwestern kenyan Plasmodium falciparum parasites. PLoS One 11: e0162524.
-
19.
Wakoli DM et al., 2022. Impact of parasite genomic dynamics on the sensitivity of Plasmodium falciparum isolates to piperaquine and other antimalarial drugs. BMC Med 20: 448.
-
20.
Muiruri P et al., 2018. Selective sweeps and genetic lineages of Plasmodium falciparum multi-drug resistance (pfmdr1) gene in Kenya. Malar J 17: 398.
-
21.
Cheruiyot AC et al., 2016. Assessment of the worldwide antimalarial resistance network standardized procedure for in vitro malaria drug sensitivity testing using SYBR green assay for field samples with various initial parasitemia levels. Antimicrob Agents Chemother 60: 2417–2424.
-
22.
Andagalu B et al., 2022. Age-dependent antibody profiles to Plasmodium antigens are differentially associated with two artemisinin combination therapy outcomes in high transmission setting. Front Med 9: 991807.
-
23.
de Laurent ZR , Chebon LJ , Ingasia LA , Akala HM , Andagalu B , Ochola-Oyier LI , Kamau E , 2018. Polymorphisms in the K13 gene in Plasmodium falciparum from different malaria transmission areas of Kenya. Am J Trop Med Hyg 98: 1360–1366.
-
24.
Yeda R , Ingasia LA , Cheruiyot AC , Okudo C , Chebon LJ , Cheruiyot J , Akala HM , Kamau E , 2016. The genotypic and phenotypic stability of Plasmodium falciparum field isolates in continuous in vitro culture. PLoS One 11: e0143565.
-
25.
Wanjala CNL , Bergmann-Leitner E , Akala HM , Odhiambo G , Ogutu BR , Andagalu B , Kamau E , Ochiel D , 2020. The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya. Malar J 19: 168.
-
26.
Mogire RM , Akala HM , Macharia RW , Juma DW , Cheruiyot AC , Andagalu B , Brown ML , El-Shemy HA , Nyanjom SG , 2017. Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets. PLoS One 12: e0186364.
-
27.
Gupta Y et al., 2022. The multistage antimalarial compound calxinin perturbates P. falciparum Ca2+ homeostasis by targeting a unique ion channel. Pharmaceutics 14: 1371.
-
28.
Miller WA III , Teye J , Achieng AO , Mogire RM , Akala H , Ong’echa JM , Rathi B , Durvasula R , Kempaiah P , Kwofie SK , 2018. Antimalarials: Review of plasmepsins as drug targets and hiv protease inhibitors interactions. Curr Top Med Chem 18: 2022–2028.
-
29.
Ohrt C et al., 2007. Establishing a malaria diagnostics centre of excellence in Kisumu, Kenya. Malar J 6: 79.
-
30.
Dhorda M et al., 2020. Towards harmonization of microscopy methods for malaria clinical research studies. Malar J 19: 324.
-
31.
Prudhomme O’Meara W et al., 2006. Systematic comparison of two methods to measure parasite density from malaria blood smears. Parasitol Res 99: 500–504.
-
32.
Gómez-Hoyos R , Cardona-Arias JA , Gutiérrez LFH , Salas-Zapata W , Carmona-Fonseca J , 2022. Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010–2022. Rev Peru Med Exp Salud Publica 39: 302–311.
-
33.
Vásquez AM , Medina AC , Tobón-Castaño A , Posada M , Vélez GJ , Campillo A , González IJ , Ding X , 2018. Performance of a highly sensitive rapid diagnostic test (HS-RDT) for detecting malaria in peripheral and placental blood samples from pregnant women in Colombia. PLoS One 13: e0201769.
-
34.
Fallis A , 2013. Malaria Microscopy Quality Assurance Manual: Version 2. Available at: https://www.who.int/docs/default-source/documents/publications/gmp/malaria-microscopy-quality-assurance-manual.pdf. Accessed August 23, 2013.
-
35.
Wanja E et al., 2017. Evaluation of a laboratory quality assurance pilot programme for malaria diagnostics in low-transmission areas of Kenya, 2013. Malar J 16: 221.
-
36.
Withers MR et al., 2006. Safety and reactogenicity of an MSP-1 malaria vaccine candidate: A randomized phase Ib dose-escalation trial in Kenyan children. PLoS Clin Trials 1: e32.
-
37.
Waitumbi JN et al., 2009. Impact of RTS,S/AS02A and RTS,S/AS01B on genotypes of P. falciparum in adults participating in a malaria vaccine clinical trial. PLoS One 4: e7849.
-
38.
Waitumbi JN , Kifude CM , Hunja CW , Ogutu BR , 2018. Females of HbAS genotype have reduced concentration of the malaria protective deoxyhemoglobin S than males. PLoS One 13: e0203455.
-
39.
Waitumbi JN , Kifude CM , Withers MR , Polhemus ME , Heppner DG , Ogutu BR , 2007. Hb G-Philadelphia or Stanleyville II? When the phenotype and genotype do not agree. Eur J Haematol 79: 177–178.
-
40.
Kifude CM , Polhemus ME , Heppner DG , Withers MR , Ogutu BR , Waitumbi JN , 2007. Hb Kenya among luo adults and young children in malaria holoendemic Western Kenya: Screened by high performance liquid chromatography and confirmed by polymerase chain reaction. Hemoglobin 31: 401–408.
-
41.
Carter N , Pamba A , Duparc S , Waitumbi JN , 2011. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J 10: 1–14.
-
42.
Manabe YC et al., 2022. Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: A prospective, multicentre, cross-sectional diagnostic accuracy study. Lancet Infect Dis 22: 1356–1364.
-
43.
Premji ZG , 2009. Coartem: The journey to the clinic. Malar J 8 (Suppl 1 ):S3.
-
44.
Medicines for Malaria Venture , 2021. Coartem Dispersible Facts. Available at: https://www.mmv.org/access/products-projects/coartem-dispersible-artemether-lumefantrine/coartem-dispersible-facts#:∼:text=Coartem. Accessed August 1, 2021.
-
45.
RTS,S Clinical Trials Partnership , 2015. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: Final results of a phase 3, individually randomised, controlled trial. Lancet 386: 31–45.
-
46.
European Medicines Agency , 2015. First malaria vaccine receives positive scientific opinion from EMA. Pharm J 295, doi: 10.1211/PJ.2015.20069061.
-
47.
Balakrishnan VS , 2021. WHO recommends malaria vaccine for children. Lancet Infect Dis 21: 1634.
-
48.
Gavi , 2023. 18 Million Doses of First-Ever Malaria Vaccine Allocated to 12 African Countries for 2023–2025: Gavi, WHO and UNICEF. Available at: https://www.gavi.org/news/media-room/18-million-doses-first-ever-malaria-vaccine-allocated-12-african-countries-2023. Accessed August 1, 2023.
-
49.
WHO , 2022. World Malaria Report 2022 .Geneva, Switzerland: World Health Organization.
-
50.
Kagoro FM , Barnes KI , Marsh K , Ekapirat N , Mercado CEG , Sinha I , Humphreys G , Dhorda M , Guerin PJ , Maude RJ , 2022. Mapping genetic markers of artemisinin resistance in Plasmodium falciparum malaria in Asia: A systematic review and spatiotemporal analysis. Lancet Microbe 3: e184–e192.
-
51.
Schmedes SE et al., 2021. Plasmodium falciparum kelch 13 mutations, 9 countries in Africa, 2014–2018. Emerg Infect Dis 27: 1902.
-
52.
Uwimana A et al., 2020. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med 26: 1602–1608.
-
53.
Bergmann C et al., 2021. Increase in kelch 13 polymorphisms in Plasmodium falciparum, southern Rwanda. Emerg Infect Dis 27: 294.
-
54.
Uwimana A et al., 2021. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: An open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis 21: 1120–1128.
-
55.
Conrad MD et al., 2023. Evolution of partial resistance to artemisinins in malaria parasites in Uganda. N Engl J Med 389: 722–732.
-
56.
Juliano JJ et al., 2023. Country Wide Surveillance Reveals Prevalent artemisinin Partial Resistance Mutations with Evidence for Multiple Origins and Expansion of High Level Sulfadoxine Pyrimethamine Resistance Mutations in Northwest Tanzania. Available at: https://doi.org/10.1101/2023.11.07.23298207. Accessed April 5, 2024.
-
57.
Stokes BH , Ward KEFD , 2022. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med 4: 1385.
-
58.
Balikagala B et al., 2021. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med 385: 1163–1171.
-
59.
Fola AA et al., 2023. Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia. Nat Microbiol 8: 1911–1919.
-
60.
Mihreteab S , Anderson K , la Fuente IM , Sutherland CJ , Smith D , Cunningham J , Beshir KB , Cheng Q , 2023. The Spread of a Validated Molecular Marker of Artemisinin Partial Resistance pfkelch13 R622I and Association with pfhrp2/3 Deletions in Eritrea. Available at: https://doi.org/10.1101/2023.10.20.23297302. Accessed April 5, 2024.
-
61.
Maniga JN et al., 2023. Novel Plasmodium falciparum k13 gene polymorphisms from Kisii County, Kenya during an era of artemisinin-based combination therapy deployment. Malar J 22: 87.
-
62.
Spalding MD , Eyase FL , Akala HM , Bedno SA , Prigge ST , Coldren RL , Moss WJ , Waters NC , 2010. Increased prevalence of the pfdhfr/phdhps quintuple mutant and rapid emergence of pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya. Malar J 9: 338.
-
63.
Mbaisi A et al., 2004. Drug susceptibility and genetic evaluation of Plasmodium falciparum isolates obtained in four distinct geographical regions of Kenya. Antimicrob Agents Chemother 48: 3598–3601.
-
64.
Juma DW et al., 2014. Trends in drug resistance codons in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Kenyan parasites from 2008 to 2012. Malar J 13: 250.
-
65.
Juma DW , Muiruri P , Yuhas K , John-Stewart G , Ottichilo R , Waitumbi J , Singa B , Polyak C , Kamau E , 2018. The prevalence and antifolate drug resistance profiles of Plasmodium falciparum in study participants randomized to discontinue or continue cotrimoxazole prophylaxis. PLoS Negl Trop Dis 13: e0007223.
-
66.
Cheruiyot J et al., 2014. Polymorphisms in Pfmdr1, Pfcrt, and Pfnhe1 genes are associated with reduced in vitro activities of quinine in Plasmodium falciparum isolates from western Kenya. Antimicrob Agents Chemother 58: 3737–3743.
-
67.
Achieng AO et al., 2015. Temporal trends in prevalence of Plasmodium falciparum molecular markers selected for by artemether-lumefantrine treatment in pre-ACT and post-ACT parasites in western Kenya. Int J Parasitol Drugs Drug Resist 5: 92–99.
-
68.
Eyase FL et al., 2013. The role of Pfmdr1 and Pfcrt in changing chloroquine, amodiaquine, mefloquine and lumefantrine susceptibility in western-Kenya P. falciparum samples during 2008–2011. PLoS One 8: e64299.
-
69.
Kamau E et al., 2015. Case report of attenuated-responsiveness to Coartem® in western Kenya. Int J Med Pharm Case Reports 2: 5–9.
-
70.
Obare P et al., 2013. Misclassification of Plasmodium infections by conventional microscopy and the impact of remedial training on the proficiency of laboratory technicians in species identification. Malar J 12: 113.
-
71.
Odhiambo F et al., 2017. Factors associated with malaria microscopy diagnostic performance following a pilot quality-assurance programme in health facilities in malaria low-transmission areas of Kenya, 2014. Malar J 16: 371.
-
72.
RTS,S Clinical Trials Partnership , 2012. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med 367: 2284–2295.
-
73.
White MT et al., 2015. Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: Secondary analysis of data from a phase 3 randomised controlled trial. Lancet Infect Dis 15: 1450–1458.
-
74.
Kamau E , Alemayehu S , Feghali KC , Juma DW , Blackstone GM , Marion WR , Obare P , Ogutu B , Ockenhouse CF , 2014. Sample-ready multiplex qPCR assay for detection of malaria. Malar J 13: 158.
-
75.
Ohrt C , O’Meara WP , Remich S , McEvoy P , Ogutu B , Mtalib R , Odera JS , 2008. Pilot assessment of the sensitivity of the malaria thin film. Malar J 7: 22.
-
76.
Morang’A C , Ayieko C , Awinda G , Achilla R , Moseti C , Ogutu B , Waitumbi J , Wanja E , 2018. Stabilization of RDT target antigens present in dried Plasmodium falciparum-infected samples for validating malaria rapid diagnostic tests at the point of care. Malar J 17: 10.
-
77.
Das D et al., 2022. Field evaluation of the diagnostic performance of EasyScan GO: A digital malaria microscopy device based on machine-learning. Malar J 21: 122.
-
78.
Horning MP et al., 2021. Performance of a fully‐automated system on a WHO malaria microscopy evaluation slide set. Malar J 20: 110.
-
79.
Wanja EW , Kuya N , Moranga C , Hickman M , Johnson JD , Moseti C , Anova L , Ogutu B , Ohrt C , 2016. Field evaluation of diagnostic performance of malaria rapid diagnostic tests in western Kenya. Malar J 15: 456.
-
80.
Stoute JA , Odindo AO , Owuor BO , Mibei EK , Opollo MO , Waitumbi JN , 2003. Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. J Infect Dis 187: 522–525.
-
81.
Korir JC , Nyakoe NK , Awinda G , Waitumbi JN , 2014. Complement activation by merozoite antigens of Plasmodium falciparum. PLoS One 9: e105093.
-
82.
Mutai BK , Waitumbi JN , 2010. Apoptosis stalks Plasmodium falciparum maintained in continuous culture condition. Malar J 9 (Suppl 3 ):S6.
-
83.
Bashir IM , Otsyula N , Awinda G , Spring M , Schneider P , Waitumbi JN , 2013. Comparison of PfHRP-2/pLDH ELISA, qPCR and microscopy for the detection of Plasmodium events and prediction of sick visits during a malaria vaccine study. PLoS One 8: e56828.
-
84.
Nyataya J , Waitumbi J , Mobegi VA , Noreddin A , El Zowalaty ME , 2020. Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions and their implications in malaria control. Diseases 8: 15.
-
85.
Andika B , Mobegi V , Gathii K , Nyataya J , Maina N , Awinda G , Mutai B , Waitumbi J , 2023. Plasmodium falciparum population structure inferred by msp1 amplicon sequencing of parasites collected from febrile patients in Kenya. Malar J 22: 263.
-
86.
Muthanje EM , Kimita G , Nyataya J , Njue W , Mulili C , Mugweru J , Mutai B , Kituyi SN , Waitumbi J , 2022. March 2019 dengue fever outbreak at the Kenyan south coast involving dengue virus serotype 3, genotypes III and V. PLOS Glob Public Health 2: e0000122.
-
87.
Nyataya J , Maraka M , Lemtudo A , Masakhwe C , Mutai B , Njaanake K , Estambale BB , Nyakoe N , Siangla J , Waitumbi JN , 2020. Serological evidence of yersiniosis, tick-borne encephalitis, West Nile, hepatitis E, Crimean-Congo hemorrhagic fever, Lyme borreliosis, and brucellosis in febrile patients presenting at diverse hospitals in Kenya. Vector Borne Zoonotic Dis 20: 348–357.
-
88.
Gathii K , Nyataya JN , Mutai BK , Awinda G , Waitumbi JN , 2018. Complete coding sequences of dengue virus type 2 strains from febrile patients seen in Malindi District Hospital, Kenya, during the 2017 dengue fever outbreak. Genome Announc 6: e00076-18.
-
89.
Davis LL , Broome ME , Cox RP , 2002. Maximizing retention in community-based clinical trials. J Nurs Scholarsh 34: 47–53.
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