title: Risk factors for Plasmodium falciparum gametocyte positivity in a longitudinal cohort.
abstract: Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined gametocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication.
authors.affiliation: Institut Pasteur, Unité de la Génétique Fonctionnelle des Maladies Infectieuses, 28 rue du Docteur Roux, F-75724 Paris cedex 15, France; Centre National de la Recherche Scientifique, URA3012, F-75015 Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Grange
authors.affiliation: Institut Pasteur, Unité de la Génétique Fonctionnelle des Maladies Infectieuses, 28 rue du Docteur Roux, F-75724 Paris cedex 15, France; Centre National de la Recherche Scientifique, URA3012, F-75015 Paris, France; Institut Pasteur de Dakar, Unité d'Epidémiologie des Maladies Infectieuses (UR 172), Dakar, Senegal.
authors.forename: Cheikh
authors.initials: C
authors.lastname: Loucoubar
authors.affiliation: Institut Pasteur, Unité de la Génétique Fonctionnelle des Maladies Infectieuses, 28 rue du Docteur Roux, F-75724 Paris cedex 15, France; Centre National de la Recherche Scientifique, URA3012, F-75015 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Telle
authors.affiliation: Institut Pasteur de Dakar, Unité d'Epidémiologie des Maladies Infectieuses (UR 172), Dakar, Senegal.
authors.forename: Adama
authors.initials: A
authors.lastname: Tall
authors.affiliation: Institut Pasteur de Dakar, Unité d'Epidémiologie des Maladies Infectieuses (UR 172), Dakar, Senegal.
authors.forename: Joseph
authors.initials: J
authors.lastname: Faye
authors.affiliation: Institut de Recherche pour le Développement, Dakar, Unité de Pathogénie Afro-Tropicale (UMR 198), Senegal.
authors.forename: Cheikh
authors.initials: C
authors.lastname: Sokhna
authors.affiliation: Institut de Recherche pour le Développement, Dakar, Unité de Pathogénie Afro-Tropicale (UMR 198), Senegal.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Trape
authors.affiliation: Institut Pasteur, Unité de la Génétique Fonctionnelle des Maladies Infectieuses, 28 rue du Docteur Roux, F-75724 Paris cedex 15, France; Centre National de la Recherche Scientifique, URA3012, F-75015 Paris, France.
authors.forename: Anavaj
authors.initials: A
authors.lastname: Sakuntabhai
authors.affiliation: Institut Pasteur, Unité de la Génétique Fonctionnelle des Maladies Infectieuses, 28 rue du Docteur Roux, F-75724 Paris cedex 15, France; Centre National de la Recherche Scientifique, URA3012, F-75015 Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bureau
authors.affiliation: Institut Pasteur, Unité de la Génétique Fonctionnelle des Maladies Infectieuses, 28 rue du Docteur Roux, F-75724 Paris cedex 15, France; Centre National de la Recherche Scientifique, URA3012, F-75015 Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Paul
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D006801:Humans; D008018:Life Cycle Stages; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology* / Q000635:transmission; D015999:Multivariate Analysis; D010963:Plasmodium falciparum / Q000254:growth & development*; D015995:Prevalence; D012307:Risk Factors; D012675:Senegal / Q000453:epidemiology
references.citation: J Infect Dis. 2002 Jun 15;185(12):1838-42
references.pmid: 12085337
references.citation: N Engl J Med. 2009 Jul 30;361(5):455-67
references.pmid: 19641202
references.citation: PLoS One. 2012;7(1):e28812
references.pmid: 22238582
references.citation: Nat Genet. 2009 Jun;41(6):657-65
references.pmid: 19465909
references.citation: Am J Trop Med Hyg. 1955 Sep;4(5):781-9
references.pmid: 13259002
references.citation: Malar J. 2004 Jun 17;3:18
references.pmid: 15202944
references.citation: Trop Med Int Health. 2004 Jan;9(1):53-61
references.pmid: 14728607
references.citation: Annu Rev Entomol. 2013;58:393-412
references.pmid: 23317045
references.citation: Nature. 1997 Jul 17;388(6639):292-5
references.pmid: 9230440
references.citation: Acta Trop. 1995 Mar;59(1):1-18
references.pmid: 7785522
references.citation: Parasitology. 2004 Sep;129(Pt 3):255-62
references.pmid: 15471001
references.citation: P N G Med J. 1986 Mar;29(1):11-7
references.pmid: 3529703
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17471-6
references.pmid: 17959777
references.citation: PLoS Med. 2012 Jan;9(1):e1001165
references.pmid: 22303287
references.citation: Am J Trop Med Hyg. 1994 Aug;51(2):123-37
references.pmid: 8074247
references.citation: Nature. 2012 Sep 20;489(7416):443-6
references.pmid: 22895189
references.citation: Am J Trop Med Hyg. 1996 Sep;55(3):350-1
references.pmid: 8842128
references.citation: Trans R Soc Trop Med Hyg. 2003 Jan-Feb;97(1):53-9
references.pmid: 12886806
references.citation: Am J Trop Med Hyg. 1999 Jun;60(6):1019-23
references.pmid: 10403336
references.citation: J Infect Dis. 1998 Mar;177(3):819-22
references.pmid: 9498474
references.citation: Trop Med Int Health. 2004 Jul;9(7):757-66
references.pmid: 15228485
references.citation: J Infect Dis. 2008 Jan 1;197(1):85-93
references.pmid: 18171290
references.citation: Theor Popul Biol. 1988 Feb;33(1):31-53
references.pmid: 2897726
references.citation: Lancet. 1996 Jun 15;347(9016):1654-8
references.pmid: 8642959
references.citation: PLoS Med. 2005 Mar;2(3):e59
references.pmid: 15719066
references.citation: Trop Med Int Health. 2007 Apr;12(4):547-53
references.pmid: 17445146
references.citation: PLoS One. 2012;7(9):e46188
references.pmid: 23029433
references.citation: PLoS One. 2007;2(1):e139
references.pmid: 17206274
references.citation: J Infect Dis. 2001 Apr 15;183(8):1254-9
references.pmid: 11262208
references.citation: Nat Genet. 2002 Jan;30(1):97-101
references.pmid: 11731797
references.citation: Am J Trop Med Hyg. 2000 Feb;62(2):210-6
references.pmid: 10813475
references.citation: Malar J. 2006;5:78
references.pmid: 16970824
references.citation: PLoS Med. 2013;10(6):e1001467
references.pmid: 23853551
references.citation: Am J Trop Med Hyg. 2007 Mar;76(3):470-4
references.pmid: 17360869
references.citation: Am J Trop Med Hyg. 1993 May;48(5):700-6
references.pmid: 8517489
references.citation: Nat Genet. 2010 Apr;42(4):328-31
references.pmid: 20305663
references.citation: PLoS One. 2008;3(4):e2000
references.pmid: 18431485
references.citation: Lancet Infect Dis. 2011 Dec;11(12):925-32
references.pmid: 21856232
references.citation: PLoS One. 2010;5(6):e11358
references.pmid: 20613877
references.citation: Malar J. 2010;9:136
references.pmid: 20497536
references.citation: Nature. 2005 Nov 24;438(7067):492-5
references.pmid: 16306991
references.citation: Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents
references.pmid: 19136431
references.citation: Parasite. 2001 Sep;8(3):243-50
references.pmid: 11584755
references.citation: J Parasitol. 2002 Feb;88(1):97-101
references.pmid: 12053988
references.citation: Clin Microbiol Rev. 2011 Apr;24(2):377-410
references.pmid: 21482730
references.citation: Nature. 2005 Nov 17;438(7066):355-9
references.pmid: 16292310
references.citation: Trans R Soc Trop Med Hyg. 1992 Jul-Aug;86(4):355-8
references.pmid: 1359683
references.citation: Infect Genet Evol. 2007 Sep;7(5):577-86
references.pmid: 17521970
references.citation: Trans R Soc Trop Med Hyg. 1986;80(1):69-77
references.pmid: 3727001
references.citation: J Exp Med. 1992 Nov 1;176(5):1311-7
references.pmid: 1402677
references.citation: BMJ Open. 2013 Jul 24;3(7):null
references.pmid: 23883878
references.citation: J Infect Dis. 2011 Jan 15;203(2):228-36
references.pmid: 21288823
references.citation: J Protozool. 1992 May-Jun;39(3):429-32
references.pmid: 1640389