Genetic differences in immune responses may affect susceptibility to mycobacterial infection, but no specific genes have been implicated in humans. We studied four children who had an unexplained genetic susceptibility to mycobacterial infection and who appeared to have inherited the same recessive mutation from a common ancestor. We used microsatellite analysis, immunofluorescence studies, and sequence analysis to study the affected patients, unaffected family members, and normal controls. A genome search using microsatellite markers identified a region on chromosome 6q in which the affected children were all homozygous for eight markers. The gene for interferon-γ receptor 1 maps to this region. Immunofluorescence studies showed that the receptor was absent on leukocytes from the affected children. Sequence analysis of complementary DNA for the gene for interferon- γ receptor 1 revealed a point mutation at nucleotide 395 that introduces a stop codon and results in a truncated protein that lacks the transmembrane and cytoplasmic domains. Four children with severe mycobacterial infections had a mutation in the gene for interferon-γ receptor 1 that leads to the absence of receptors on cell surfaces and a functional defect in the up-regulation of tumor necrosis factor α by macrophages in response to interferon-γ. The interferon-γ pathway is important in the response to intracellular pathogens such as mycobacteria.

The attenuated strain of Mycobacterium bovis bacille Calmette–Guérin (BCG) is the most widely used vaccine in the world. In most children, inoculation of live BCG vaccine is harmless although it occasionally leads to a benign regional adenitis.¹ In rare cases, however, vaccination causes disseminated BCG infection, which may be lethal. Impaired immunity of the host is generally thought to be the pathogenic mechanism. Disseminated BCG infection has been reported in children with inherited immune disorders. Most of these children had severe combined immunodeficiency, which is characterized by an absence of T cells, and some had chronic granulomatous disease, which is marked by an impairment of the phagocyte respiratory burst.^2,3 Rare cases of BCG infection have also been reported in association with the acquired immunodeficiency syndrome.²

Adrian Hill and colleagues report a genome-wide association study for tuberculosis in cohorts from Ghana and The Gambia. They identify a host susceptibility loci for pulmonary tuberculosis disease at 18q11.2. We combined two tuberculosis genome-wide association studies from Ghana and The Gambia with subsequent replication in a combined 11,425 individuals. rs4331426, located in a gene-poor region on chromosome 18q11.2, was associated with disease (combined P = 6.8 × 10−9, odds ratio = 1.19, 95% CI = 1.13–1.27). Our study demonstrates that genome-wide association studies can identify new susceptibility loci for infectious diseases, even in African populations, in which levels of linkage disequilibrium are particularly low.

Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.

Data obtained in animals indicate that neonatal immune responses are biased toward Th2. This could reduce the efficacy of vaccines against viral and mycobacterial diseases. The ability of human newborns to develop a Th1 immune response upon immunization has not been studied. Since the vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers a Th1-type response in adults, we investigated whether it induces a similar response in newborns and whether age at vaccination influences immunogenicity. We found that BCG vaccination at birth induces a memory Th1-type response of similar magnitude to that when given later in life. This study demonstrates that human newborns can be immunized against pathogens controlled by a Th1 immune response.