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The Lancet Global Health. Causes of non-malarial fever in Laos: a prospective study
[Source: The Lancet Global Health, full text: (LINK). Abstract, edited.]
Mayfong Mayxay MD a b c, Jos?e Castonguay-Vanier MSc a, Vilada Chansamouth MD a, Audrey Dubot-P?r?s PhD a c d, Daniel H Paris MD c e, Rattanaphone Phetsouvanh MD a c, Jarasporn Tangkhabuanbutra MSc e, Phouvieng Douangdala MD f, Saythong Inthalath MD f, Phoutthalavanh Souvannasing MD g, G?nther Slesak MD h, Narongchai Tongyoo MPhil e, Anisone Chanthongthip a, Phonepasith Panyanouvong a, Bountoy Sibounheuang a, Koukeo Phommasone MD a, Michael Dohnt I j, Darouny Phonekeo MD k, Bouasy Hongvanthong MD l, Sinakhone Xayadeth k, Pakapak Ketmayoon MSc m, Stuart D Blacksell PhD c e, Catrin E Moore PhD a c, Scott B Craig PhD i j, Mary-Anne Burns i j, Prof Frank von Sonnenburg MD n, Andrew Corwin PhD o, Prof Xavier de Lamballerie MD d, Iveth J Gonz?lez MD p, Eva Maria Christophel MD q, Amy Cawthorne MSc q, David Bell MRCP p, Dr Paul N Newton MRCP a c
Summary
Background
Because of reductions in the incidence of Plasmodium falciparum malaria in Laos, identification of the causes of fever in people without malaria, and discussion of the best empirical treatment options, are urgently needed. We aimed to identify the causes of non-malarial acute fever in patients in rural Laos.
Methods
For this prospective study, we recruited 1938 febrile patients, between May, 2008, and December, 2010, at Luang Namtha provincial hospital in northwest Laos (n=1390), and between September, 2008, and December, 2010, at Salavan provincial hospital in southern Laos (n=548). Eligible participants were aged 5?49 years with fever (≥38?C) lasting 8 days or less and were eligible for malaria testing by national guidelines.
Findings
With conservative definitions of cause, we assigned 799 (41%) patients a diagnosis. With exclusion of influenza, the top five diagnoses when only one aetiological agent per patient was identified were dengue (156 [8%] of 1927 patients), scrub typhus (122 [7%] of 1871), Japanese encephalitis virus (112 [6%] of 1924), leptospirosis (109 [6%] of 1934), and bacteraemia (43 [2%] of 1938). 115 (32%) of 358 patients at Luang Namtha hospital tested influenza PCR-positive between June and December, 2010, of which influenza B was the most frequently detected strain (n=121 [87%]). Disease frequency differed significantly between the two sites: Japanese encephalitis virus infection (p=0?04), typhoid (p=0?006), and leptospirosis (p=0?001) were more common at Luang Namtha, whereas dengue and malaria were more common at Salavan (all p<0?0001). With use of evidence from southeast Asia when possible, we estimated that azithromycin, doxycycline, ceftriaxone, and ofloxacin would have had significant efficacy for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of patients, respectively.
Interpretation
Our findings suggest that a wide range of treatable or preventable pathogens are implicated in non-malarial febrile illness in Laos. Empirical treatment with doxycycline for patients with undifferentiated fever and negative rapid diagnostic tests for malaria and dengue could be an appropriate strategy for rural health workers in Laos.
Funding
Wellcome Trust, WHO?Western Pacific Region, Foundation for Innovative New Diagnostics, US Centers for Disease Control and Prevention.
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a Lao Oxford Mahosot Hospital Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos; b Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; c Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; d UMR_D 190 ?Emergence des Pathologies Virales?, Aix-Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France; e Mahidol?Oxford Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok; f Luang Namtha Provincial Hospital, Luang Namtha, Luang Namtha Province, Laos; g Salavan Provincial Hospital, Salavan, Salavan Province, Laos; h Tropical Hospital Paul-Lechler-Krankenhaus, T?bingen, Germany; i WHO/FAO/OIE Collaborating Centre for Leptospirosis Reference and Research, Queensland, Australia; j School of Biomedical Sciences, Queensland University of Technology, Queensland, Australia; k National Centre for Laboratory and Epidemiology, Vientiane, Laos; l Centre for Malariology, Parasitology, and Entomology, Vientiane, Laos; m WHO, Vientiane, Laos; n Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; o Centers for Disease Control and Prevention, US Embassy, Vientiane, Laos; p Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland; q WHO?Regional Office for the Western Pacific, Manila, Philippines
Correspondence to: Dr Paul Newton, Lao Oxford Mahosot Hospital Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos
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The Lancet Global Health, Volume 1, Issue 1, Pages e46 - e54, July 2013
doi:10.1016/S2214-109X(13)70008-1
Copyright ? 2013 Mayxay et al. Open Access article distributed under the terms of CC BY Published by Elsevier Ltd. All rights reserved.
Causes of non-malarial fever in Laos: a prospective study
Original Text
doi:10.1016/S2214-109X(13)70008-1
Copyright ? 2013 Mayxay et al. Open Access article distributed under the terms of CC BY Published by Elsevier Ltd. All rights reserved.
Causes of non-malarial fever in Laos: a prospective study
Original Text
Mayfong Mayxay MD a b c, Jos?e Castonguay-Vanier MSc a, Vilada Chansamouth MD a, Audrey Dubot-P?r?s PhD a c d, Daniel H Paris MD c e, Rattanaphone Phetsouvanh MD a c, Jarasporn Tangkhabuanbutra MSc e, Phouvieng Douangdala MD f, Saythong Inthalath MD f, Phoutthalavanh Souvannasing MD g, G?nther Slesak MD h, Narongchai Tongyoo MPhil e, Anisone Chanthongthip a, Phonepasith Panyanouvong a, Bountoy Sibounheuang a, Koukeo Phommasone MD a, Michael Dohnt I j, Darouny Phonekeo MD k, Bouasy Hongvanthong MD l, Sinakhone Xayadeth k, Pakapak Ketmayoon MSc m, Stuart D Blacksell PhD c e, Catrin E Moore PhD a c, Scott B Craig PhD i j, Mary-Anne Burns i j, Prof Frank von Sonnenburg MD n, Andrew Corwin PhD o, Prof Xavier de Lamballerie MD d, Iveth J Gonz?lez MD p, Eva Maria Christophel MD q, Amy Cawthorne MSc q, David Bell MRCP p, Dr Paul N Newton MRCP a c
Summary
Background
Because of reductions in the incidence of Plasmodium falciparum malaria in Laos, identification of the causes of fever in people without malaria, and discussion of the best empirical treatment options, are urgently needed. We aimed to identify the causes of non-malarial acute fever in patients in rural Laos.
Methods
For this prospective study, we recruited 1938 febrile patients, between May, 2008, and December, 2010, at Luang Namtha provincial hospital in northwest Laos (n=1390), and between September, 2008, and December, 2010, at Salavan provincial hospital in southern Laos (n=548). Eligible participants were aged 5?49 years with fever (≥38?C) lasting 8 days or less and were eligible for malaria testing by national guidelines.
Findings
With conservative definitions of cause, we assigned 799 (41%) patients a diagnosis. With exclusion of influenza, the top five diagnoses when only one aetiological agent per patient was identified were dengue (156 [8%] of 1927 patients), scrub typhus (122 [7%] of 1871), Japanese encephalitis virus (112 [6%] of 1924), leptospirosis (109 [6%] of 1934), and bacteraemia (43 [2%] of 1938). 115 (32%) of 358 patients at Luang Namtha hospital tested influenza PCR-positive between June and December, 2010, of which influenza B was the most frequently detected strain (n=121 [87%]). Disease frequency differed significantly between the two sites: Japanese encephalitis virus infection (p=0?04), typhoid (p=0?006), and leptospirosis (p=0?001) were more common at Luang Namtha, whereas dengue and malaria were more common at Salavan (all p<0?0001). With use of evidence from southeast Asia when possible, we estimated that azithromycin, doxycycline, ceftriaxone, and ofloxacin would have had significant efficacy for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of patients, respectively.
Interpretation
Our findings suggest that a wide range of treatable or preventable pathogens are implicated in non-malarial febrile illness in Laos. Empirical treatment with doxycycline for patients with undifferentiated fever and negative rapid diagnostic tests for malaria and dengue could be an appropriate strategy for rural health workers in Laos.
Funding
Wellcome Trust, WHO?Western Pacific Region, Foundation for Innovative New Diagnostics, US Centers for Disease Control and Prevention.
________
a Lao Oxford Mahosot Hospital Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos; b Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos; c Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; d UMR_D 190 ?Emergence des Pathologies Virales?, Aix-Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France; e Mahidol?Oxford Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok; f Luang Namtha Provincial Hospital, Luang Namtha, Luang Namtha Province, Laos; g Salavan Provincial Hospital, Salavan, Salavan Province, Laos; h Tropical Hospital Paul-Lechler-Krankenhaus, T?bingen, Germany; i WHO/FAO/OIE Collaborating Centre for Leptospirosis Reference and Research, Queensland, Australia; j School of Biomedical Sciences, Queensland University of Technology, Queensland, Australia; k National Centre for Laboratory and Epidemiology, Vientiane, Laos; l Centre for Malariology, Parasitology, and Entomology, Vientiane, Laos; m WHO, Vientiane, Laos; n Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; o Centers for Disease Control and Prevention, US Embassy, Vientiane, Laos; p Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland; q WHO?Regional Office for the Western Pacific, Manila, Philippines
Correspondence to: Dr Paul Newton, Lao Oxford Mahosot Hospital Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos