Efficacy of oseltamivir treatment started within 5 days of symptom onset to
reduce influenza illness duration and virus shedding in an urban setting in
Bangladesh: a randomised placebo-controlled trial.
Author(s): Fry AM(1), Goswami D(2), Nahar K(2), Sharmin AT(2), Rahman M(2), Gubareva L(3),
Azim T(2), Bresee J(3), Luby SP(4), Brooks WA(2).
Affiliation(s): Author information:
(1)Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Electronic address: afry@cdc.gov.
(2)International Centre for Diarrhoreal Disease Research Bangladesh, Dhaka,
Bangladesh.
(3)Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
(4)Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA;
International Centre for Diarrhoreal Disease Research Bangladesh, Dhaka,
Bangladesh.
Publication date & source: 2014, Lancet Infect Dis. , 14(2):109-18
BACKGROUND: Influenza causes substantial morbidity and mortality worldwide. Few
data exist for the efficacy of neuraminidase inhibitors, which are the only
readily available influenza treatment options, especially in low-income settings.
We assessed the efficacy of treatment with the neuraminidase inhibitor
oseltamivir to reduce patient illness and viral shedding in people with
influenza, in whom treatment was started within 5 days of symptom onset, in an
urban setting in Bangladesh.
METHODS: We undertook a double-blind, randomised, controlled trial between May,
2008, and December, 2010. Patients with a positive rapid influenza test
identified by surveillance of households in Kamalapur, Bangladesh were randomly
allocated on a 1:1 basis to receive oseltamivir or placebo twice daily for 5
days. Randomisation lists for individuals enrolled less than 48 h and 48 h or
longer since illness onset were generated with permuted blocks of variable length
between two and eight. Participants and study staff were masked to treatment
group. Participants provided nasal wash specimens at enrolment and 2, 4, and 7
days later, and were visited daily to record symptoms. All specimens were tested
for influenza with reverse-transcriptase PCR, and if the result was positive, we
isolated the virus. The primary endpoints were duration of clinical illness and
viral shedding in patients treated less than and more than 48 h since illness
onset and the frequency of oseltamivir resistance during treatment. Analyses were
intention to treat unless otherwise specified. This trial is registered with
ClinicalTrials.gov, number NCT00707941.
FINDINGS: Overall, 1190 people with a median age of 5 years (IQR 2-9) were
enrolled: 794 (67%) less than 48 h since symptom onset and 396 (33%) 48 h or
longer since symptom onset. 592 participants were assigned to placebo and 598 to
oseltamivir. The median duration of symptoms was shorter in the oseltamivir group
(3 days, IQR 1-5) than in the placebo group (4 days, 1-6; p=0.01). When
stratified by timing of treatment initiation, in participants enrolled 48 h or
longer since illness onset, the median duration of symptoms was similar in both
groups (oseltamivir 3 days [IQR 2-5], placebo 3 days [1-5]; p=0.04). The median
duration of symptoms was reduced by 1 day in the group given oseltamivir who were
enrolled less than 48 h since symptom onset compared with those given placebo,
but this difference was not significant. In those with all swab specimens
(n=1134), oseltamivir significantly reduced virus isolation on days 2 (placebo
374 [66%] vs oseltamivir 321 [56%]; difference 15.2%, 95% CI 9.5-20.8, p=0.0004),
4 (241 [43%] vs 174 [30%]; difference 30.2%, 95% CI 24.6-35.8, p<0.0001), and 7
(68 [12%] vs 36 [6%]; difference 47.5%, 95% CI 44.2-50.8, p=0.0009). In
participants enrolled 48 h or longer since illness onset, oseltamivir treatment
significantly reduced virus isolation on days 2 and 4, but not day 7. In
participants enrolled less than 48 h since illness onset, oseltamivir treatment
significantly reduced virus isolation on days 2, 4, and 7. The emergency of
resistance to oseltamivir during treatment was rare overall (<1%) and in
influenza A H1N1pdm09 viruses (3.9%).
INTERPRETATION: Oseltamivir treatment resulted in a modest reduction in the
duration of symptoms and virus shedding in people with uncomplicated influenza
infections, even when treatment was started 48 h or longer after illness onset.
FUNDING: Centers for Disease Control and Prevention (in agreement with the
International Centre for Diarrhoeal Disease Research, Bangladesh).
|