Page 396 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHAPtER 26 Host Defenses to Intracellular Bacteria 377

Leprosy Gastroenteritis
Mycobacterium leprae is most likely transmitted by contact S. enterica serovars Typhimurium and Enteritidis, often referred
with patients who shed microorganisms in nasal secretions and to as nontyphoidal salmonella (NTS), are the major causes of
lesion exudates. It primarily affects the nerves and the skin, salmonella gastroenteritis in humans, which occurs mainly as a
frequently leading to stigmatizing deformities. In skin, bacilli result of the ingestion of contaminated food or water. The bacteria
target keratinocytes, histiocytes, and macrophages, whereas rapidly cross the intestinal epithelia and replicate in the lamina
in peripheral nerves, Schwann cells are the major target for propria, inducing an influx of polymorphonuclear neutrophils
entry. Leprosy is a spectral disease. The tuberculoid pole is (PMNs), which is generally sufficient to resolve the infection
characterized by rigorous T-cell responses, which succeed in within 7 days. In rare cases, bacteria enter the bloodstream and
restricting microbial growth in well-defined lesions contain- cause systemic bacteremia, most notably in patients with AIDS,
ing few bacilli. In contrast, at the lepromatous pole, bacterial where death can occur as a result of septic shock. 8
growth is unrestricted and lesions contain abundant bacilli
within macrophages lacking signs of activation. Several types Listeriosis
of immunosuppression have been implicated in this latter type Listeriosis monocytogenes is increasingly recognized to cause
of disease. Infection of Schwann cells promotes nerve damage foodborne gastroenteritis. Clinical listeriosis affects mainly
and anesthesia. This results in injuries and secondary infections pregnant women, older adults, fetuses, and neonates. Disease
that significantly exaggerate the disease. Despite the success of manifestations are most severe in patients with a compromised
multidrug therapy in reducing the number of registered leprosy immune system, in whom the CNS becomes involved and fatal
cases worldwide, some 216 000 new cases were reported in bacteremia can result. Additionally, as these bacteria are able to
2013. This suggests that active transmission of M. leprae is still cross the placenta, listeriosis is a major cause of perinatal and
occurring and that more effective interventions are required to neonatal disease, typically resulting in abortion. Listeria outbreaks
prevent it. 4 are sporadic with low incidence but high fatality and affect
high-income countries, such as the United States.
Atypical Mycobacterial Infections
Mycobacterial species present in the environment are typi- Brucellosis
cally unable to persist within activated macrophages and thus Brucellosis is the most common global zoonosis of humans with
9
rarely cause disease in individuals with competent immune approximately 500 000 cases per year. It is caused by Brucella
status. 5 abortus, B. melitensis, or B. suis, which primarily infect cows,
As a consequence of human immunodeficiency virus (HIV) goats, and pigs, respectively. The bacteria are transmitted to
infection, however, nontuberculous mycobacteria (NTM), primar- humans via inhalation, through abraded skin or the GI tract.
ily Mycobacterium avium/Mycobacterium intracellulare, have Lesions are primarily found within macrophage-rich tissues,
gained clinical importance, and these infections are recognized especially the spleen and bone marrow. Human brucellosis is
as one of the most common complications of AIDS in industrial- characterized by systemic symptoms, particularly undulant fever.
ized nations. Although the disease often remains subclinical, it becomes chronic
Mycobacterium scrofulaceum occasionally causes lymphadenitis in some patients, and relapses and remissions may occur. Interest
in children, and Mycobacterium kansasii primarily causes infec- in brucellosis has increased in the last 5 years because of elevated
tions in older men with preexisting lung disease. levels of detection resulting from better surveillance.
Mycobacterium ulcerans causes a severe subcutaneous infection
characterized by chronic skin ulcerations, known as Buruli ulcer. Lymphogranuloma Venereum
This pathology is caused—at least in part—by elaboration of a Lymphogranuloma venereum (LGV), a sexually transmitted
mycolactone toxin by the bacillus that exhibits highly cytopathic disease, is highly prevalent in Africa, Southeast Asia, and Latin
6
effects. Buruli ulcer is most predominant in West African America. LGV has recently emerged as infection of sexually active
countries that accounted for most of the 2251 cases reported homosexual men in Europe and the United States. It is caused
globally in 2014. 7 by the L1, L2, and L3 serotypes of Chlamydia trachomatis, which
are disseminated from the urogenital tract to local lymph nodes
Typhoid or Enteric Fever and then to skin. Accordingly, LGV is characterized by lymph
Salmonella enterica serovars Typhi and Paratyphi A, Paratyphi node swelling and skin lesions, which are accompanied by systemic
B, and Paratyphi C are leading causes of community-acquired complications. 10
bloodstream infections in low- and middle-income countries.
The route of transmission is fecal–oral and largely occurs via Melioidosis
contaminated water sources. Bacteria are disseminated within Burkholderia pseudomallei is a gram-negative bacillus and the
mononuclear phagocytes (MPs) from the GI tract to macrophage- causative agent of melioidosis, endemic in Southeast Asia and
rich organs, particularly the liver, spleen, and lymph nodes. Northern Australia. The disease can be acquired through inhala-
Accordingly, typhoid is characterized by systemic symptoms, tion and ingestion or through cuts in the skin. Susceptible hosts
such as prolonged fever and malaise, with sustained bacteremia, can suffer abscess formation in multiple organs and, in some cases,
although diarrhea or constipation may also be present. In some disseminated infection, resulting in septic shock accompanied by
cases, an asymptomatic carrier state can persist as a result of pneumonia. There are an estimated 165 000 cases of melioidosis
chronic infection of the gallbladder, which maintains the envi- per year globally, resulting in approximately 89 000 deaths. 11
ronmental reservoir of infection in endemic areas. Typhoid fever
remains a major cause of morbidity and mortality, with approxi- Tularemia
mately 21 million new cases and over 190 000 deaths per year This rare zoonosis in humans caused by Francisella tularensis is
worldwide. 8 mainly found in rabbits and has recently gained wider recognition