title: Acute undifferentiated febrile illness in rural Cambodia: a 3-year prospective observational study.
abstract: In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects.
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, University of Munich, Munich, Germany.
authors.forename: Tara C
authors.initials: TC
authors.lastname: Mueller
authors.affiliation: National Center for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
authors.forename: Sovannaroth
authors.initials: S
authors.lastname: Siv
authors.affiliation: Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
authors.forename: Nimol
authors.initials: N
authors.lastname: Khim
authors.affiliation: Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
authors.forename: Saorin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, University of Munich, Munich, Germany.
authors.forename: Erna
authors.initials: E
authors.lastname: Fleischmann
authors.affiliation: Parasitology and Mycology Department, Institut Pasteur, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ariey
authors.affiliation: Virology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.affiliation: Medical Laboratory, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guillard
authors.affiliation: Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland.
authors.forename: Iveth J
authors.initials: IJ
authors.lastname: González
authors.affiliation: WHO Regional Office for the Western Pacific (WPRO), Manila, Philippines.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Christophel
authors.affiliation: WHO Country Office, Phnom Penh, Cambodia.
authors.forename: Rashid
authors.initials: R
authors.lastname: Abdur
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, University of Munich, Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: von Sonnenburg
authors.affiliation: Intellectual Ventures Laboratory, Seattle, Washington, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.affiliation: Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
authors.forename: Didier
authors.initials: D
authors.lastname: Menard
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D002160:Cambodia / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D060085:Coinfection / Q000097:blood / Q000150:complications / Q000453:epidemiology; D003715:Dengue / Q000097:blood / Q000150:complications / Q000453:epidemiology; D005260:Female; D005335:Fever of Unknown Origin / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007251:Influenza, Human / Q000097:blood / Q000150:complications / Q000453:epidemiology; D007922:Leptospirosis / Q000097:blood / Q000150:complications / Q000453:epidemiology; D008288:Malaria / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic; D012424:Rural Population; D055815:Young Adult
chemical_list: D011933:Reagent Kits, Diagnostic; D002097:C-Reactive Protein
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