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376 PARt tHREE Host Defenses to Infectious Agents

TABLE 26.1 Major Infectious Diseases Caused by Intracellular Bacteria
Disease Pathogen Prevalence Incubation time Route of Infection target Cell
Granulomatous Intracellular Bacteria
Tuberculosis Mycobacterium tuberculosis Worldwide Years (latency after Inhalation of Macrophage
primary infection and bacteria-containing
disease reactivation) microdroplets
Weeks (miliary TB)
Leprosy Mycobacterium leprae South America Years Smear infection Macrophage
Africa through mucosa/ Schwann cell
India inhalation
Southeast Asia
Typhoid fever Salmonella enterica serovars Worldwide 7–10 days Fecal–oral Macrophage
Typhi and Paratyphi
Brucellosis Brucella spp. Worldwide Weeks to months Zoonosis; cows, Macrophage
goats, pigs;
inhalation, gut, skin
abrasion
Listeriosis Listeria monocytogenes Worldwide Days to months Fecal–oral Macrophage
Hepatocyte
Nongranulomatous Intracellular Bacteria
Legionnaires’ disease Legionella pneumophila Worldwide 2–10 days Inhalation Macrophage
Rocky Mountain Rickettsia rickettsiae Western 1 week Tick bite Vascular endothelial cell
spotted fever hemisphere Smooth muscle cell
Urogenital infection Chlamydia trachomatis Worldwide 1–3 weeks Sexual intercourse Epithelial cell
serovars D-K
Conjunctivitis, Chlamydia trachomatis Africa Conjunctivitis: 1–3 weeks Eye Epithelial cell
trachoma serovars A-C Trachoma: years
Cat scratch disease Bartonella henselae Worldwide Bacillary angiomatosis Flea, sandfly, Erythrocyte
B. quintana Peliosis hepatitis or mosquito bite; Endothelial cell
B. bacilliformis Endocarditis animal scratch or
Bacteremia with fever bite
Neuroretinitis: 1–3 weeks

the serovars Typhi and Paratyphi are not restricted to the carrier state or the so-called latent TB infection (LTBI). Infection
gastrointestinal (GI) tract but are disseminated to internal organs, with M. tuberculosis starts with the so-called Ghon complex,
primarily the liver and spleen. In these cases, the type of clinical characterized by a caseous lesion in the midlung as well as in
disease depends markedly on the infected tissue type. the draining lymph nodes. These primary lesions can progress,
2
but their development rarely causes disease directly. Moreover,
KEY CONCEPtS bacteria from these sites can disseminate to other regions of
Characteristic Features of Intracellular the lung and systemically, causing disease of the kidneys, liver,
Bacterial Infections and central nervous system (CNS). Containment of the primary
lesions, which leads to LTBI, is a function of an effective, pre-
Persistence of bacteria inside mononuclear phagocytes (i.e., dominately cellular antitubercular immune response. Infection
macrophages) of immunocompromised patients, notably those with acquired
Low to absent bacterial-mediated toxicity to the host immunodeficiency syndrome (AIDS), or newborns frequently
Protection requires cytokine-mediated activation of infected results in systemic disease (miliary TB). TB represents a major
phagocytes health problem worldwide, including an increasing incidence
Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) produced by
antigen-specific T cells are key cytokines for protection in many industrialized countries. In 2015, the World Health
Organization (WHO) estimated that 10.4 million active TB
cases were diagnosed worldwide and close to 1.8 million people
3
died of the disease. The much larger estimated number of 2
INTRACELLULAR BACTERIAL INFECTIONS OF billion individuals infected with M. tuberculosis well illustrates
CLINICAL RELEVANCE (Table 26.1) the dissociation of infection from disease. The emergence of
multidrug-resistant strains and extremely drug-resistant strains
Granulomatous Infections has complicated treatment with currently available antibiotic
Tuberculosis therapy, and even when treatment is successful, recurrence
The major entry of tubercle bacilli into the human body is via of disease can occur. The currently available live whole cell
inhalation into the lung. These inhaled bacteria are then engulfed vaccine BCG (Bacille Calmette–Guérin), an attenuated strain
by alveolar macrophages, which transport the pathogens to the derived from the etiological agent of bovine TB Mycobacte-
lung interstitia. Their exact fate after these events is enigmatic. rium bovis, shows only low and variable protection against
Moreover, most infections in humans result in an asymptomatic pulmonary TB.