Infections in the compromised host

30 Infections in the compromised host


The human body has a complex system of protective mechanisms to prevent infection. This involves both the adaptive (cellular and humoral) immune system and the innate defence system (e.g. skin, mucous membranes). (These have been described in detail in Chapters 910 and 11.) So far, we have concentrated on the common and serious infections occurring in people whose protective mechanisms are largely intact. In these circumstances, the interactions between host and parasite are such that the parasite has to use all its guile to survive and invade the host, and the healthy host is able to combat such an invasion. The focus of this chapter involves the infections that arise when the host defences are compromised, resulting in the host–parasite equation being weighted heavily in favour of the parasite.

The compromised host

Compromised hosts are people with one or more defects in their body’s natural defences against microbial invaders. Consequently they are much more liable to suffer from severe and life-threatening infections. Modern medicine has effective methods for treating many types of cancers, is improving organ transplantation techniques and has developed technology that enables people with otherwise fatal diseases to lead prolonged and productive lives. A consequence of these achievements, however, is an increasing number of compromised people prone to infection. In addition, viral infections including HIV and HTLV result in a compromised immune system referred to as AIDS and adult T-cell leukaemia/lymphoma (ATLL), respectively.

Secondary defects of innate defences include disruption of the body’s mechanical barriers

A variety of factors can disrupt the mechanical non-specific barriers to infection. For example, burns, traumatic injury and major surgery destroy the continuity of the skin and may leave poorly vascularized tissue near the body surface, providing a relatively defenceless site for microbes to colonize and invade. In health, the mucosal barriers of the respiratory and alimentary tract are vital to prevent infection. Damage sustained, for example, through endoscopy, surgery or radiotherapy, provides easy access for infecting organisms. Devices such as intravascular and urinary catheters, or procedures such as lumbar puncture or bone marrow aspiration, allow organisms to bypass the normal defences and enter normally sterile parts of the body. Foreign bodies such as prostheses, e.g. hip joints or heart valves, and cerebrospinal fluid (CSF) shunts alter the local non-specific host responses and provide surfaces that microbes can colonize more readily than the natural equivalents.

The adage ‘obstruction leads to infection’ is a valuable reminder that the defences of many body systems work partly through the clearance of undesirable materials, e.g. by urine flow, ciliary action in the respiratory tract, and peristalsis in the gut. Interference with these mechanisms as a result of pathologic obstruction, central nervous system dysfunction or surgical intervention tends to result in infection.

Primary adaptive immunodeficiency results from defects in the primary differentiation environment or in cell differentiation

The major congenital abnormalities arising in the adaptive immune system are depicted in Figure 30.2. A defect in the stromal microenvironment in which lymphocytes differentiate may lead to failure to produce B cells (Bruton-type agammaglobulinaemia) or T cells (DiGeorge syndrome).

Differentiation pathways themselves may also be affected. For example, a non-functional recombinase enzyme will prevent the recombination of gene fragments that form the B-cell antibody or the T-cell receptor variable regions for antigen recognition, with a resulting severe combined immunodeficiency (SCID).

The most common form of congenital antibody deficiency – common variable immunodeficiency – is characterized by recurrent pyogenic infections and is probably heterogeneous. Although the number of immature B cells in the marrow tends to be normal, the peripheral B cells are either low in number or in some cases absent. Where present, they are unable to differentiate into plasma cells in some cases or to secrete antibody in others.

Transient hypogammaglobulinaemia of infancy, characterized by recurrent respiratory infections, is associated with a low serum IgG concentration, which often normalizes abruptly by 3–4    years of age (Fig. 30.3).

Immunoglobulin deficiency occurs naturally in human infants as the maternal serum IgG concentration decays. It is a serious problem in very premature babies as, depending on the gestational age, maternal IgG may not have crossed the placental barrier.

Causes of secondary adaptive immunodeficiency include malnutrition, infections, neoplasia, splenectomy and certain medical treatments

Worldwide, malnutrition is common and the most important cause of acquired immunodeficiency. The major form, protein–energy malnutrition (PEM) presents as a wide range of disorders, with kwashiorkor and marasmus at the two poles. It results in:

Infections themselves are often immunosuppressive (see Table 30.2), and none is more so than HIV infection, which gives rise to AIDS (see Ch. 21). Neoplasia of the lymphoid system frequently induces a state of reduced immunoreactivity, and splenectomy, for whatever reason, results in impaired humoral responses.

Treatment of disease can also cause immunosuppression. For example:

Therefore a patient receiving treatment for neoplastic disease will be immunocompromised as a result of both the disease and the treatment.

It is important to recognize immunodeficiencies and to understand which procedures are likely to compromise the natural defences of a patient. Due to improvements in medical technology, many immune defects, particularly immunosuppression resulting from radiotherapy or cytotoxic drugs, are transient, and patients who survive the period of immunosuppression have a good chance of a complete recovery.

Infections of the host with deficient innate immunity due to physical factors

Burn wound infections

Burns damage the body’s mechanical barriers, neutrophil function and immune responses

Burn wounds are sterile immediately after the burn is inflicted, but inevitably become colonized within hours with a mixed bacterial flora. Burn injuries cause direct damage to the mechanical barriers of the body and abnormalities in neutrophil function and immune responses. In addition, there is a major physiologic derangement with loss of fluids and electrolytes. The burn provides a highly nutritious surface for organisms to colonize, and the incidence of serious infection varies with the size and depth of the burn and the age of the patient. Topical antimicrobial therapy should prevent infection of burns of    <       30% of the total body area, but larger burns are always colonized. Non-invasive infection is confined to the eschar, which is the non-viable skin debris on the surface of deep burns. It is characterized by rapid separation of the eschar from the underlying tissue and a heavy exudate of purulent material from the burn wound. The systemic symptoms are usually relatively mild. However, organisms can invade from heavily colonized burn eschars into viable tissue beneath and rapidly destroy the tissue, converting partial-thickness burns into full skin-thickness destruction. From here, it is a small step to invasion of the lymphatics and thence to the bloodstream or direct invasion of blood vessels, and to septicaemia. Septicaemia in patients with burns is often polymicrobial.

Traumatic injury and surgical wound infections

Both accidental and intentional trauma destroy the integrity of the body surface and leave it liable to infection. Accidental injury may result in microbes being introduced deep into the wound. The species involved will depend upon the nature of the wound, as discussed in Chapter 26.

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Jul 9, 2017 | Posted by in MICROBIOLOGY | Comments Off on Infections in the compromised host

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