The Lancet Global Health (Jul 2013)

Causes of non-malarial fever in Laos: a prospective study

  • Mayfong Mayxay, MD,
  • Josée Castonguay-Vanier, MSc,
  • Vilada Chansamouth, MD,
  • Audrey Dubot-Pérès, PhD,
  • Daniel H Paris, MD,
  • Rattanaphone Phetsouvanh, MD,
  • Jarasporn Tangkhabuanbutra, MSc,
  • Phouvieng Douangdala, MD,
  • Saythong Inthalath, MD,
  • Phoutthalavanh Souvannasing, MD,
  • Günther Slesak, MD,
  • Narongchai Tongyoo, MPhil,
  • Anisone Chanthongthip,
  • Phonepasith Panyanouvong,
  • Bountoy Sibounheuang,
  • Koukeo Phommasone, MD,
  • Michael Dohnt,
  • Darouny Phonekeo, MD,
  • Bouasy Hongvanthong, MD,
  • Sinakhone Xayadeth,
  • Pakapak Ketmayoon, MSc,
  • Stuart D Blacksell, PhD,
  • Catrin E Moore, PhD,
  • Scott B Craig, PhD,
  • Mary-Anne Burns,
  • Prof. Frank von Sonnenburg, MD,
  • Andrew Corwin, PhD,
  • Prof. Xavier de Lamballerie, MD,
  • Iveth J González, MD,
  • Eva Maria Christophel, MD,
  • Amy Cawthorne, MSc,
  • David Bell, MRCP,
  • Dr. Paul N Newton, MRCP

DOI
https://doi.org/10.1016/S2214-109X(13)70008-1
Journal volume & issue
Vol. 1, no. 1
pp. e46 – e54

Abstract

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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.