Host-Pathogen Interactions in Emerging and Re-emerging Infectious Diseases: A Genomic Perspective of Tuberculosis, Malaria, Human Immunodeficiency Virus Infection, Hepatitis B, and Cholera

Abstract

On exposure to a pathogen, a host may resist infection, become subclinically infected, or progress through several stages from mild to severe infection. Chronic sequelae may or may not occur. Host factors, particularly host genes, influence many of these stages. We have used a model of the continuum of pathogenesis of infectious diseases to consider the effect of host genes on five pathogens of significant public health burden: Mycobacterium tuberculosis, Plasmodium species, human immunodeficiency virus, hepatitis B virus, and Vibrio cholerae. The relationships between these infections and polymorphisms in human leukocyte antigen, cytokines, other immune response, or pathogen receptor genes are reviewed. We discuss gene-gene interactions and their effects in complex settings, such as coinfections with several pathogens. Priorities for prevention and control of these pathogens include vaccines and antimicrobial drugs. Research on how host genes can influence vaccine responses and the efficacy of drugs or other interventions, as well as further research into the relationship of host genes to infectious disease outcomes, may lead to new strategies for prevention and control.

Association of Gene Polymorphisms and Serum Levels of IL-18 with the Susceptibility to Infection with Hepatitis B Virus

“…The gene loci for cytokines are defined, and polymorphisms of cytokine genes are suggested to influence the outcome of HBV infection [6]. Therefore, many recent studies have focused on the effect of gene polymorphisms of cytokines on disease outcome such as prediction of infection risk, disease progression, chronicity and response to vaccination and treatment as well as vertical transmission [7][8][9][10].…”

Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome

“…The relation between immune response gene variation and disease outcomes may be clarified by the analysis of polymorphic variations in individual 'candidate genes' deduced to be of direct importance in disease pathogenesis. [10][11][12] This approach has been applied extensively to mycobacterium spp. infections and has linked disease severity either in individuals, or susceptibility of subpopulations to infection, with polymorphic variants within a number of genes, including natural resistance associated macrophage protein (NRAMP1), mannose-binding lectin (MBL), vitamin D receptor (VDR) and various cytokine genes.…”

Taking Stock: Relating Theory to Experiment

“…Just as with the current HIV, both the medieval Plague and the 1918 epidemic of Spanish Flu had major impacts on human populations and significantly altered the course of human history (McNeill 1976). Increased contacts with faunal elements (e.g., rodents), tradesmen, colonizers, and soldiers were at the root of new diseases that had ravaging effects on endemic populations (Diamond 1997).…”

“…It carved a path of death through Europe, once Genoese tradesmen, who contracted the disease in the Crimea, introduced it in 1346. Within 4 years it had moved to Scandinavia and even entered Greenland, killing a third of the European population on its way, according to the medieval chronicler Froissart (McNeill 1976). This 14th century Plague was not a unique event: other Great Plagues have occurred over the past 2 500 years in Asia, the Middle East, North Africa, and Europe and the disease continues to cause 200 reported deaths per year worldwide (Tikhomirov 2001).…”