Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.
BACKGROUND
Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings.


METHODS
We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations.


RESULTS
Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events.


CONCLUSIONS
In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.
PATH, Seattle, WA, USA; University of Washington, Departments of Global Health and Medicine, Seattle, WA, USA. Electronic address: jrortiz@uw.edu.
Justin R
JR
Ortiz
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Doli
D
Goswami
PATH, Seattle, WA, USA.
Kristen D C
KD
Lewis
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Amina Tahia
AT
Sharmeen
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Moshtaq
M
Ahmed
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Mustafizur
M
Rahman
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Mohammed Z
MZ
Rahman
PATH, Seattle, WA, USA.
Jodi
J
Feser
PATH, Seattle, WA, USA; University of Washington, Departments of Global Health and Medicine, Seattle, WA, USA.
Kathleen M
KM
Neuzil
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; Johns Hopkins University, Baltimore, MD, USA.
W Abdullah
WA
Brooks
D001459:Bangladesh; D002675:Child, Preschool; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D012135:Respiratory Sounds; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects
D007252:Influenza Vaccines; D010919:Placebos; D014613:Vaccines, Attenuated
Clinical trial; Live attenuated influenza vaccine