Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

Abstract

Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

Local Cutaneous Complications After Bacille Calmette-Guerin Vaccine: Experience of a Single Center

“…Local ulceration at the vaccination site, suppurative lymphadenitis, osteitis, osteomyelitis, and disseminated BCG infection are severe complications which occur in approximately two cases per 1 million vaccinations [14]. Severe complications are more seen in patients with immunodeficiency disorders [15,16]. Susceptibility to infections increases in patients with primary immune deficiency.…”

“…Especially children with T cells deficiency have high risk for mycobacterial infections. Severe combined immunodeficiency (SCID), chronic granulomatous disease, complete DiGeorge syndrome, Mendelian susceptibility to mycobacterial disease and acquired immunodeficiency syndrome are some diseases which have increased risk for disseminated BCG infections [16,17]. In addition, M. tuberculosis is an important cause of morbidity and mortality in HIV-infected children [16].…”

Interferon-gamma-dependent Immunity in Bacillus Calmette-Guérin Vaccine Osteitis Survivors

“…1 Host immunity and variation especially in innate immunity influence the risk to get TB and other mycobacterial diseases. 2,3 After phagocytosis of mycobacteria, macrophages produce different mediators like interleukin-1 (IL-1) which enhance the maturation of dendritic cells, and IL-12 which enhance the maturation of T helper type-1 (Th1) cells, further promoting the production of interferon-gamma (IFN-γ). 4 …”

Loculated empyema due to tuberculosis in a child

“…Due to the lack of lymphadenitis and parenchymal disease as well as unusual aggressive course of the infection with M. tuberculosis , other causes of primary immunodeficiency must be considered. This included HIV and primary immunodeficiency and conditions with a lack of interferon-gamma (IFN-γ) production 3. This child did not have a history of previous infections suggestive of immunodeficiency.…”