Infections in the Immunocompromised

Recap the basics of the immune system

I took an entire unit on immunology last year, so you can read all about the immune system here. Otherwise, read on for the tl;dr version.

The main types of immunity are innate and adaptive immunity. Innate immunity includes anatomical barriers such as skin, the complement system, normal flora and cells such as NK cells, monocytes and neutrophils. Adaptive immunity is more specific, but needs to be primed by a previous encounter by that pathogen. Adaptive cells include the antibody-producing B-cells, as well as T-cells. T-cells come in two main flavours: the helper variety (CD4+), which mediate immune responses, and the cytotoxic variety (CD8+), which induce death of cells that have been infected by viruses.

T-helper cells can be further divided into different kinds of T-cells. In this post, we will only be looking at Th1 and Th2 cells. Th1 cells respond mainly to intracellular pathogens and viruses, and are characterised by IFNγ production. They activate macrophages and induce B-cells to make opsonising and complement-fixing antibodies, leading to "cell-mediated immunity." Th2 cells, on the other hand, respond to extracellular antigens. They are characterised by IL-4 release and activate B-cells, which make neutralising antibodies, leading to "humoral immunity."

Describe what happens when a patient’s immune system is compromised

If your immune system is compromised, you get sick more often (duh). The types of pathogens that you are more likely to get depends on the component of your immune system that is defective. If neutrophils are defective, you are more likely to get staphs, streps and some fungi such as Candida, if you have globulin defects, you are more likely to get encapsulated bacteria and Giardia, and if your skin is broken in some way (e.g. IV lines, catheters etc.) you are more likely to get S. aureus, S. pyogenes, Candida, and so on. Some immune defects, like a defect in cell-mediated immunity, predisposes you to infection from a range of different organisms.

Infections in the cancer patient (aka febrile neutropenia)

Neutropenia, a deficiency in neutrophils, may occur as a result of chemotherapy. Neutropenia can be mild (1000-1500 cells/μL), moderate (500-1000 cells/μL) or severe (less than 500 cells/μL). If a patient with severe neutropenia has a temperature of greater than 38.3°C, or a temperature of greater than 38°C for over an hour, they are considered to have neutropenic fever. Risk factors for neutropenic fever include severity and duration of neutropenia, cancer not in remission and mucositis (a side-effect of chemotherapy). Neutropenic fever, particularly neutropenic sepsis, is considered to be a medical emergency as infection can progress very quickly. Prompt empiric antibiotics are usually given as there is roughly 10% mortality per hour delay in antibiotic therapy.

Antibiotic therapy needs to be relatively broad-spectrum as a large proportion of patients (~1/2) will not have a pathogen identified. The most common bacteria in neutropenic fever are Gram-positive organisms such as S. aureus and S. epidermidis, but Gram-negative bacteria used to be more common. The pathogen associated with the highest rate of mortality is Pseudomonas, so antibiotic therapy must include cover for Pseudomonas. A commonly-used antibiotic for this purpose is Pipericillin-Tazobactam (tazocin).

If fever persists despite antibiotic therapy, other causative agents, such as fungi, should be considered. The main candidate is Candida, as risk factors for candidaemia include severe neutropenia, use of broad-spectrum antibiotics and mucocutaneous damage. Other common fungi include moulds such as Aspergillus, Fusarium and Zygomycetes, which are particularly prevalent following bone marrow transplant. These moulds usually cause pulmonary infections, but may also cause CNS or skin infections.

To diagnose the causative agent of neutropenic fever, blood cultures are usually done. Cultures are done from peripheral blood as well as from ports of IV catheters. Sputum, urine and other targeted samples may also be used. Chest X-rays and CT scans might be used to check for other signs of illness.

Neutropenic infection can be prevented in several different ways. Firstly, patients should be placed in a positive pressure room, free of flowers that might carry spores. A modified diet should be given, and prophylactic drugs may also be given if deemed necessary.

Infections in transplant patients

See previous post: Allograft-Transmissible Infections

Infections in splenectomy patients (sepsis)

The spleen is important for a variety of immune functions, including being the site of maturation of IgM memory B-cells, sequestering opsonised encapsulated bacteria, and modulating the effects of cytokines. Hence, removal of the spleen predisposes to a variety of infections, particularly by encapsulated bacteria such as S. pneumoniae, N. meningitidis and H. influenzae. Roughly 5% of splenectomy patients will experience an overwhelming post-splenectomy infection (OPSI) at some point, usually caused by S. pneumoniae. The greatest risk for OPSI is in the 6 months following splenectomy. Most deaths from OPSI occur within the first 24 hours of becoming unwell. OPSI can be treated with vaccination, lifelong antibiotics and extra emergency antibiotics.

The effects of acquired immune deficiency after infection by HIV

Since CD4+ cells are targeted by HIV, HIV severely weakens the immune system. Therefore, HIV/AIDS patients are at risk of many opportunistic infections. As their immune system gets weaker (CD4+ cell count decreases), they become at risk of a greater variety of infections. Here's a quick list of some opportunistic infections seen in HIV/AIDS patients:

• Kaposi's sarcoma: Related to Human Herpes Virus 8 (HHV8). It forms lesions on the skin. If untreated, it affects all organs except for the brain.
• Cytomegalovirus (CMV/HHV5): Many adults are seropositive for CMV (a.k.a. HHV5), but it is only reactivated when CD4 cell counts fall below 100. CMV may manifest as CMV retinitis in HIV/AIDS patients.
• Cryptosporidium parvum: Cryptosporidium is a protozoan that can cause acute and chronic diarrhoea. It can be life-threatening in HIV patients.
• Pneumocystis jirovecii pneumonia: Caused by a fungus. Common opportunistic infection in HIV/AIDS patients.
• Tuberculosis: Many HIV patients are co-infected with TB. TB is becoming more drug-resistant, which is a problem.
• Cryptococcus neoformans meningitis: Cryptococcus is a yeast-like fungus that can cause meningitis when CD4 counts fall below 100.
• Toxoplasma gondii cerebral toxoplasmosis: Toxoplasma is a protozoan spread in cat faeces and meat. It can cause cysts that are dormant in the brain, but are activated when CD4 counts fall below 100.