title: Submicroscopic Plasmodium prevalence in relation to malaria incidence in 20 villages in western Cambodia.
abstract: Cambodia has seen a marked reduction in the incidence of Plasmodium falciparum over the past decade without a corresponding decline in Plasmodium vivax incidence. It is unknown to what extent local transmission is sustained by a chain of clinical and sub-clinical infections or by continued re-introduction via migration. Using an ultrasensitive molecular technique, 20 villages in western Cambodia were surveyed to detect the low season prevalence of P. falciparum and P. vivax and local treatment records were reviewed.
  
  
  
  During March to May 2015 cross-sectional surveys were conducted in 20 villages in Battambang, western Cambodia. Demographic and epidemiological data and venous blood samples were collected from 50 randomly selected adult volunteers in each village. Blood was tested for Plasmodium infections by rapid diagnostic test (RDT), microscopy and high volume (0.5 ml packed red blood cell) quantitative polymerase chain reaction (uPCR). Positive samples were analysed by nested PCR to determine the Plasmodium species. Malaria case records were collected from the Provincial Health Department and village malaria workers to determine incidence and migration status.
  
  
  
  Among the 1000 participants, 91 (9.1%) were positive for any Plasmodium infection by uPCR, seven (0.7%) by microscopy, and two (0.2%) by RDT. uPCR P. vivax prevalence was 6.6%, P. falciparum 0.7%, and undetermined Plasmodium species 1.8%. Being male (adjusted OR 2.0; 95% CI 1.2-3.4); being a young adult <30 years (aOR 2.1; 95% CI 1.3-3.4); recent forest travel (aOR 2.8; 95% CI 1.6-4.8); and, a history of malaria (aOR 5.2; 95% CI 2.5-10.7) were independent risk factors for parasitaemia. Of the clinical malaria cases diagnosed by village malaria workers, 43.9% (297/634) and 38.4% (201/523) were among migrants in 2013 and in 2014, respectively. Plasmodium vivax prevalence determined by uPCR significantly correlated with vivax malaria incidences in both 2014 and 2015 (p = 0.001 and 0.002, respectively), whereas no relationship was observed in falciparum malaria (p = 0.36 and p = 0.59, respectively).
  
  
  
  There was heterogeneity in the malaria parasite reservoir between villages, and Plasmodium prevalence correlated with subsequent malaria incidence. The association was attributable chiefly to P. vivax infections, which were nine-fold more prevalent than P. falciparum infections. In the absence of a radical cure with 8-aminoquinolines, P. vivax transmission will continue even as P. falciparum prevalence declines. Migration was associated with over a third of incident cases of clinical malaria. Trial registration clinicaltrials.gov (NCT01872702). Registered 4 June 2013.
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand. Rupam@tropmedres.ac.|Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Rupam@tropmedres.ac.
authors.forename: Rupam
authors.identifier: 0000-0002-3281-9702
authors.initials: R
authors.lastname: Tripura
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Peto
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Christianne C
authors.initials: CC
authors.lastname: Veugen
authors.affiliation: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
authors.forename: Chea
authors.initials: C
authors.lastname: Nguon
authors.affiliation: Provincial Health Department, Battambang, Cambodia.
authors.forename: Chan
authors.initials: C
authors.lastname: Davoeung
authors.affiliation: Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: James
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|World-Wide Antimalarial Resistance Network, Mahidol University, Bangkok, Thailand.
authors.forename: Mehul
authors.initials: M
authors.lastname: Dhorda
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.|Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Maude
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jureeporn
authors.initials: J
authors.lastname: Duanguppama
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Krittaya
authors.initials: K
authors.lastname: Patumrat
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Lorenz
authors.initials: L
authors.lastname: von Seidlein
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, Rajthevee, Bangkok, 10400, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
mesh_terms: D000328:Adult; D000368:Aged; D058345:Asymptomatic Infections / Q000453:epidemiology; D002160:Cambodia / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015994:Incidence; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000302:isolation & purification; D015995:Prevalence; D012424:Rural Population; D055815:Young Adult
keywords: Asymptomatic; Cambodia; Malaria; Plasmodium Falciparum; Plasmodium vivax; Sub-clinical; Sub-microscopic; uPCR