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Published in: Trials 1/2017

Open Access 01-12-2017 | Study protocol

Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled trial

Authors: Victoria Nankabirwa, James K. Tumwine, Olive Namugga, Thorkild Tylleskär, Grace Ndeezi, Bjarne Robberstad, Mihai G. Netea, Halvor Sommerfelt

Published in: Trials | Issue 1/2017

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Abstract

Background

Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB). It is unclear whether BCG vaccination very early in life offers adequate protection against TB and other infections among HIV-1-exposed children because even those who remain uninfected with HIV-1 show signs of impaired immunocompetence early in infancy. This study will compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV-1-exposed infants.

Methods

This is an individually randomized controlled trial in 2200 HIV-1-exposed infants. The intervention is BCG vaccination within 24 h of birth while the comparator is BCG given at 14 weeks of age. The study co-primary outcomes are severe illness in the first 14 weeks of life, and production of tumor necrosis factor, interleukin (IL)-1β, IL-6 and interferon-γ in response to mycobacterial and nonmycobacterial antigens. The study is being conducted in three health centers in Uganda.

Discussion

A well-timed BCG vaccination could have important nonspecific effects in HIV-1-exposed infants. This trial could inform the development of appropriate timing of BCG vaccination for HIV-1-exposed infants.

Trial registration

ClinicalTrials.gov, identifier: NCT02606526. Registered on 12 November 2015.
Appendix
Available only for authorised users
Footnotes
1
Among children aged below 2 months of age, severe illness (other than TB) will be defined as illness that is associated with any of the following danger signs observed or verified by a study clinician: inability to feed or vomiting of everything, lethargy or unconsciousness, severe lower chest in-drawing, axillary temperature of ≥37.5 °C or <35.5 °C, grunting, cyanosis, convulsions or a history of convulsions, and/or results in hospitalization and/or results in death.
Among children aged 2 months of age or older, severe illness (other than TB) will be defined as illness that: is associated with at least one of the following danger signs observed or verified by a study clinician: inability to drink or breastfeed, lethargy or unconsciousness, vomiting of all feeds, convulsions or a history of convulsions, and/or results in hospitalization and/or results in death. Hospitalization and death resulting from violent injury or burns will not contribute to the severe illness definition.
 
2
In infants from whom a blood culture was not performed or in whom a blood culture was negative, clinical sepsis is signaled by one of our study physicians (VN, ON, JKT or GN) having initiated treatment for sepsis or confirmed that such treatment was appropriate and/or by a positive sepsis screen. A positive sepsis screen is the presence of any two of the following: total leukocyte count <5000/mm3; absolute neutrophil count <1500/mm3; band cell:neutrophil count ratio >0.2; both of two C-reactive protein serum levels in specimens taken 24 h to 48 h apart >1 mg/dl.
 
3
Confirmed sepsis is signaled by a blood culture that is positive for bacteria known to cause infant sepsis.
 
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Metadata
Title
Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled trial
Authors
Victoria Nankabirwa
James K. Tumwine
Olive Namugga
Thorkild Tylleskär
Grace Ndeezi
Bjarne Robberstad
Mihai G. Netea
Halvor Sommerfelt
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-1881-z

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