Background Because of reductions in the incidence of Plasmodium falciparum malaria in Laos, identifi cation 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 defi nitions of cause, we assigned 799 (41%) patients a diagnosis. With exclusion of
infl uenza, the top fi ve diagnoses when only one aetiological agent per patient was identifi ed 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
infl uenza PCR-positive between June and December, 2010, of which infl uenza B was the most frequently detected
strain (n=121 [87%]). Disease frequency diff ered signifi cantly 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 ofl oxacin would have had signifi cant effi cacy
for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of patients, respectively.
Interpretation Our fi ndings suggest that a wide range of treatable or preventable pathogens are implicated in nonmalarial
febrile illness in Laos. Empirical treatment with doxycycline for patients with undiff erentiated 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 Pacifi c Region, Foundation for Innovative New Diagnostics, US Centers for
Disease Control and Prevention
