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Nat Commun. 2019 Mar 29;10(1):1433. doi: 10.1038/s41467-019-09441-1.

The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density.

Author information

1
MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK. hslater@path.org.
2
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, 4002, Switzerland.
3
University of Basel, Basel, 4001, Switzerland.
4
Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, 4002, Switzerland.
5
Vector-borne Diseases Unit, Papua New Guinea Institute for Medical Research, Madang, Papua New Guinea.
6
Division of Population Health and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, VIC, Australia.
7
Medical Biology, University of Melbourne, Melbourne, 3010, VIC, Australia.
8
Disease Elimination, Burnet Institute, Melbourne, 3004, VIC, Australia.
9
MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
10
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
11
Malaria Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77, Stockholm, Sweden.
12
Département de Sciences Biomédicales, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208, Burkina Faso.
13
Institute for Disease Modeling, Intellectual Ventures, Bellevue, 98005, Washington, USA.
14
Department of Training and Research, Mnazi Mmoja Hospital, Zanzibar, Tanzania.
15
Population Health and Immunity Division, Walter and Eliza Hall Institute, Melbourne, 3052, Victoria, Australia.
16
Department of Biological Sciences, University of Notre Dame, Indiana, 46556, USA.
17
Department of Parasites and Insect Vectors, Institut Pasteur, Paris, 75015, France.
18
Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, 6525, The Netherlands.
19
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
20
Institute of Biotechnology, Addis Ababa University, Addis Ababa, Ethiopia.
21
Diagnostics Program, PATH, Seattle, Washington, 98121, United States of America.
22
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
23
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, University of Oxford, Oxford, OX3 7BN, UK.
24
Institute of Health, University of Health and Allied Sciences, Hohoe, PMB 31, Ghana.
25
Sorbonne Université, INSERM, Institut Pierre-Louis d'Epidémiologie et de Santé Publique, AP- HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Parasitologie-Mycologie, Paris, 75646, France.
26
Malaria Research and Training Centre, Parasitic Diseases Epidemiology Department, UMI 3189, University of Sciences, Technique and Technology, Bamako, Mali.
27
Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
28
Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Global Health, Centers for Disease Control and Prevention, Atlanta, 30030, GA, United States of America.
29
National Institute for Medical Research, Mwanza Medical Research Centre, Mwanza, Tanzania.
30
Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208, Burkina Faso.
31
Department of Disease Control, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
32
Malaria Elimination Initiative, Global Health Group, University of California, San Francisco, San Francisco, 94158, CA, United States.
33
Biological Sciences Department, Dar es Salaam University College of Education, P. O. Box 2329, Dar es Salaam, Tanzania.
34
Institut Pasteur de Dakar, Laboratoire d'Entomologie Médicale, Dakar, Senegal.
35
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
36
Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
37
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
38
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, 63110, Thailand.
39
Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
40
MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK.

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.

PMID:
30926893
PMCID:
PMC6440965
DOI:
10.1038/s41467-019-09441-1
[Indexed for MEDLINE]
Free PMC Article

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