Abstract

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.

The role of subpatent infections for malaria transmission and elimination is unclear. Here, Slater et al. analyse several malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections.

Details

Title
The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density
Author
Slater, Hannah C 1 ; Ross, Amanda 2   VIAFID ORCID Logo  ; Felger Ingrid 3 ; Hofmann, Natalie E 3 ; Robinson, Leanne 4 ; Cook, Jackie 5 ; Gonçalves, Bronner P 6 ; Björkman, Anders 7 ; Ouedraogo, Andre Lin 8 ; Morris, Ulrika 9   VIAFID ORCID Logo  ; Mwinyi, Msellem 10 ; Koepfli Cristian 11 ; Mueller, Ivo 12 ; Tadesse Fitsum 13 ; Gadisa Endalamaw 14 ; Das, Smita 15 ; Domingo Gonzalo 15 ; Kapulu Melissa 16 ; Midega Janet 16 ; Owusu-Agyei Seth 17 ; Nabet Cécile 18 ; Piarroux Renaud 18 ; Ogobara, Doumbo 19 ; Doumbo Safiatou Niare 19 ; Koram Kwadwo 20 ; Lucchi, Naomi 21 ; Udhayakumar Venkatachalam 21 ; Jacklin, Mosha 22 ; Tiono Alfred 23 ; Chandramohan, Daniel 24 ; Gosling Roly 25 ; Felista, Mwingira 26 ; Sauerwein, Robert 27 ; Paul, Richard 28 ; Riley, Eleanor M 29   VIAFID ORCID Logo  ; White, Nicholas J 30 ; Nosten Francois 31   VIAFID ORCID Logo  ; Imwong Mallika 32 ; Bousema Teun 33 ; Drakeley, Chris 6   VIAFID ORCID Logo  ; Okell, Lucy C 1   VIAFID ORCID Logo 

1  Imperial College London, MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
2  Swiss Tropical and Public Health Institute, Department of Epidemiology and Public Health, Basel, Switzerland (GRID:grid.416786.a) (ISNI:0000 0004 0587 0574); University of Basel, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
3  University of Basel, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); Swiss Tropical and Public Health Institute, Medical Parasitology and Infection Biology, Basel, Switzerland (GRID:grid.416786.a) (ISNI:0000 0004 0587 0574) 
4  Papua New Guinea Institute for Medical Research, Vector-borne Diseases Unit, Madang, Papua New Guinea (GRID:grid.417153.5) (ISNI:0000 0001 2288 2831); The Walter and Eliza Hall Institute of Medical Research, Division of Population Health and Immunity, Parkville, Australia (GRID:grid.1042.7); University of Melbourne, Medical Biology, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Disease Elimination, Burnet Institute, Melbourne, Australia (GRID:grid.1056.2) (ISNI:0000 0001 2224 8486) 
5  London School of Hygiene and Tropical Medicine, MRC Tropical Epidemiology Group, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
6  Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
7  Malaria Research, Department of Microbiology, Tumor and Cell Biology, Stockholm, Sweden (GRID:grid.8991.9) 
8  Centre National de Recherche et de Formation sur le Paludisme, Département de Sciences Biomédicales, Ouagadougou, Burkina Faso (GRID:grid.418150.9); Institute for Disease Modeling, Intellectual Ventures, Bellevue, USA (GRID:grid.471104.7) (ISNI:0000 0004 0406 7608) 
9  Malaria Research, Department of Microbiology, Tumor and Cell Biology, Stockholm, Sweden (GRID:grid.471104.7) 
10  Mnazi Mmoja Hospital, Department of Training and Research, Zanzibar, Tanzania (GRID:grid.471104.7) 
11  Walter and Eliza Hall Institute, Population Health and Immunity Division, Melbourne, Australia (GRID:grid.1042.7); University of Notre Dame, Department of Biological Sciences, Indiana, USA (GRID:grid.131063.6) (ISNI:0000 0001 2168 0066) 
12  The Walter and Eliza Hall Institute of Medical Research, Division of Population Health and Immunity, Parkville, Australia (GRID:grid.1042.7); Institut Pasteur, Department of Parasites and Insect Vectors, Paris, France (GRID:grid.428999.7) (ISNI:0000 0001 2353 6535); University of Melbourne, Medical Biology, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
13  Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382); Armauer Hansen Research Institute, Addis Ababa, Ethiopia (GRID:grid.418720.8) (ISNI:0000 0000 4319 4715); Addis Ababa University, Institute of Biotechnology, Addis Ababa, Ethiopia (GRID:grid.7123.7) (ISNI:0000 0001 1250 5688) 
14  Armauer Hansen Research Institute, Addis Ababa, Ethiopia (GRID:grid.418720.8) (ISNI:0000 0000 4319 4715) 
15  Diagnostics Program, PATH, Seattle, Washington, United States of America (GRID:grid.263306.2) (ISNI:0000 0000 9949 9403) 
16  University of Oxford, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Oxford, KEMRI–Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya, Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
17  University of Health and Allied Sciences, Institute of Health, Hohoe, Ghana (GRID:grid.449729.5) 
18  Groupe Hospitalier Pitié-Salpêtrière, Service de Parasitologie-Mycologie, Sorbonne Université, INSERM, Institut Pierre-Louis d’Epidémiologie et de Santé Publique, AP- HP, Paris, France (GRID:grid.411439.a) (ISNI:0000 0001 2150 9058) 
19  University of Sciences, Technique and Technology, Malaria Research and Training Centre, Parasitic Diseases Epidemiology Department, UMI 3189, Bamako, Mali (GRID:grid.411439.a) 
20  University of Ghana, Noguchi Memorial Institute for Medical Research, Legon, Ghana (GRID:grid.8652.9) (ISNI:0000 0004 1937 1485) 
21  Centers for Global Health, Centers for Disease Control and Prevention, Malaria Branch, Division of Parasitic Diseases and Malaria, Atlanta, United States of America (GRID:grid.416738.f) (ISNI:0000 0001 2163 0069) 
22  Mwanza Medical Research Centre, National Institute for Medical Research, Mwanza, Tanzania (GRID:grid.416738.f) 
23  Centre National de Recherche et de Formation sur le Paludisme, Department of Biomedical Sciences, Ouagadougou, Burkina Faso (GRID:grid.418150.9) 
24  London School of Hygiene and Tropical Medicine, Department of Disease Control, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
25  University of California, San Francisco, Malaria Elimination Initiative, Global Health Group, San Francisco, United States (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
26  Dar es Salaam University College of Education, Biological Sciences Department, Dar es Salaam, Tanzania (GRID:grid.8193.3) (ISNI:0000 0004 0648 0244) 
27  Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382) 
28  Laboratoire d‘Entomologie Médicale, Institut Pasteur de Dakar, Dakar, Senegal (GRID:grid.10417.33) 
29  Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X); University of Edinburgh, Easter Bush, The Roslin Institute and Royal (Dick) School of Veterinary Studies, Midlothian, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
30  Nuffield Department of Clinical Medicine, University of Oxford, Centre for Tropical Medicine and Global Health, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); Faculty of Tropical Medicine, Mahidol University, Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand (GRID:grid.10223.32) (ISNI:0000 0004 1937 0490) 
31  Nuffield Department of Clinical Medicine, University of Oxford, Centre for Tropical Medicine and Global Health, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Shoklo Malaria Research Unit, Mae Sot, Thailand (GRID:grid.10223.32) (ISNI:0000 0004 1937 0490) 
32  Faculty of Tropical Medicine, Mahidol University, Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand (GRID:grid.10223.32) (ISNI:0000 0004 1937 0490); Faculty of Tropical Medicine, Mahidol University, Department of Molecular Tropical Medicine and Genetics, Bangkok, Thailand (GRID:grid.10223.32) (ISNI:0000 0004 1937 0490) 
33  Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X); Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-09441-1
ProQuest document ID
2199873574
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.