Elsevier

Vaccine

Volume 29, Issue 9, 17 February 2011, Pages 1727-1730
Vaccine

Short communication
Mycobacterium bovis (Bacille Calmette-Guérin) bacteremia in immunocompetent neonates following vaccination

https://doi.org/10.1016/j.vaccine.2010.12.089Get rights and content

Abstract

We describe four cases of Mycobacterium tuberculosis complex bacteremia diagnosed in immunocompetent neonates, who presented with high fever and/or jaundice within 72 h after Bacille Calmette-Guérin (BCG) vaccination. All neonates were hospitalized, and none received anti-mycobacterial therapy. All recovered completely and remain healthy 2–3.5 years later. Genotyping of one available isolate identified the pathogen as Mycobacterium bovis BCG. The similar clinical presentations and close temporal association between BCG vaccination and illness suggest that all four neonates likely had BCG bacteremia. BCG bacteremia shortly following vaccination among healthy neonates has not been previously described and merits further study to determine its frequency and clinical significance.

Section snippets

Background

Bacille Calmette-Guerin (BCG) vaccine is one of the world's oldest and most widely used vaccines and is part of national immunization programs in over 172 countries [1]. The World Health Organization (WHO) recommends BCG vaccination for all infants without known HIV infection or other immunocompromising conditions in countries with a high tuberculosis (TB) burden [2], [3]. Global BCG coverage exceeds 80% with approximately 100 million children vaccinated annually [1], [3]. In Thailand, BCG

Case reports (Table 1)

Cases were diagnosed in hospitals participating in a surveillance project run collaboratively by the Thailand Ministry of Public Health and the U.S. Centers for Disease Control and Prevention (CDC). Blood cultures were collected from all children with suspected sepsis with a goal of inoculating two bottles: a standard aerobic pediatric FAN® bottle (PF bottle) and a bottle optimized for mycobacterial detection (MB bottle), which were incubated for up to 42 days. During 2007–2008, 1816 infants

Epidemiologic investigations

Epidemiologic investigations were conducted for each case to confirm the diagnosis and determine potential common source exposures. Initial evaluation centered on concerns about congenital or nosocomial TB infection. Neither the mothers nor any household members reported signs or symptoms of recent TB infection or disease, or any illness compatible with TB disease.

Reviews to exclude the possibility of culture contamination or accidental specimen swapping were conducted in both case hospitals

Confirmation of M. bovis BCG

A subculture of the MTB complex isolate from Patient 1 was shipped to the Mycobacteriology Laboratory at the U.S. CDC, Atlanta, GA for genotypic analysis. Results of in-house assays, including RD1 analysis and spoligotyping, confirmed that the isolate was M. bovis BCG.

Patient follow-up

The first three patients were re-evaluated at 1 year of age and Patient 4 at 2 months of age. All of the children appeared healthy, with normal physical examinations and age-appropriate development. Chest radiographs were normal and repeat blood cultures were negative in all four children. Each child had a scar at their BCG vaccination site. Parent interviews by phone or in person with all four patients between ages 2–3.5 years confirmed no health concerns.

Discussion

Our findings support that these cases were causally linked to BCG vaccination. First, the temporal association with vaccination was consistent, with symptoms occurring within 72 h after vaccination in all cases. Second, a causal association is biologically plausible, as BCG vaccination is a live, attenuated vaccine designed to incite an immune response by actively replicating after administration. Third, alternative explanations are limited in immunocompetent patients with healthy, HIV-negative

Acknowledgement

We thank Dr. Dina Pfeifer of the World Health Organization for her critical review of the manuscript and insightful commentary.

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