growing number of immunocompromised

[Guest guest]

The growing number of immunocompromised By H. Kahn

Bulletin of the Atomic Scientists 7 January 2008

It's estimated that about 10 million people in the United States (3.6

percent of the population) are immunocompromised. But that's likely an

underestimate because it only includes those with HIV/AIDS (diagnosed

and undiagnosed), organ transplant recipients, and cancer patients;

there's a sizable population that takes immunosuppressive drugs for

other disorders such as rheumatoid arthritis and inflammatory bowel

disease.

This is a concern because while modern medicine allows many

immunocompromised individuals to live longer, they're at an increased

risk for acquiring and spreading infections to others. For example,

because those with HIV are at high risk for acquiring and developing

active tuberculosis, the HIV/AIDS pandemic has led to a resurgence in

tuberculosis, which could now be spread (tuberculosis is transmissable

through the air) to other high-risk immunocompromised individuals such

as those with chronic renal failure. (See " Tuberculosis and HIV

Infection: The Global Setting " and " Tuberculosis Transmission in a

Renal Dialysis Center--Nevada, 2003. " In addition, because a number of

people have been inadequately treated against tuberculosis, a deadly

drug-resistant form of the disease is becoming widespread. (See my

December column, " The Scourge of Antibiotic-Resistant Bacteria. " )

Agents of bioterrorism such as smallpox also pose a great risk to the

immunocompromised, who are ineligible for the smallpox vaccine because

it contains an active (although weakened) virus that could cause a

deadly adverse reaction.

The biodefense challenge posed by the immunocompromised hasn't gone

unnoticed. In 2005, U.S. officials at the National Institutes of

Health awarded a number of academic institutions research grants to

investigate the molecular basis for differing immune capabilities.

However, we should prioritize ways in which to prevent people from

becoming immunocompromised in the first place. Public health programs

such as HIV prevention and primary care of hypertension and diabetes,

which can lead to organ failure and transplantation, would help reduce

the number of immunocompromised each year.

A brief explanation of the immune system

The immune system is incredibly complex with many cooperating

components. (See " Understanding the Immune System: How It Works "

[PDF].) It's akin to a vast army, consisting of surveillance,

artillery, communications, and special forces. And like an army,

there's the danger of friendly fire: The body must make sure it

launches an attack against an invader rather than against itself. When

it mistakenly attacks itself, autoimmune diseases such as rheumatoid

arthritis (the body attacks the joints) and diabetes mellitus type 1

(the body attacks the pancreas) can develop.

Blood possesses both red blood cells and white blood cells. The white

blood cells fight invaders; in particular, one type of white blood

cell, the lymphocyte, plays a key role in the body's defense. There

are several types of lymphocytes, including T cells and B cells. T

helper cells work in communications by serving as an important relay

messenger between other T and B cells. For example, T helper cells

stimulate T killer cells to directly kill invaders, and they activate

B cells to secrete antibodies. B cells' antibodies coat invaders and

mark them for destruction. Different B cells secrete different

antibodies for different invaders. Vaccines prepare B cells to

recognize specific deadly invaders such as the smallpox, polio, and

measles viruses and secrete unique antibodies against them. B cells

need to see these pathogens enough times to remember that when they

encounter them, they're ready to launch their missiles. This is the

rationale behind booster shots.

Phagocytes (phago meaning " eat " and cyte meaning " cell " ), another type

of white blood cell, eat the invaders. Some phagocytes destroy the

invaders after ingesting them; others destroy invaders by spraying

chemicals at them.

Another important component of the immune system is a series of 25

proteins, collectively known as " complement. " Like reservists, these

proteins float around in the blood waiting to get activated, at which

point they form an attack complex. However, if one protein is missing,

the system doesn't work well and can make the individual prone to

infections.

In addition, different cells around the body secrete chemicals (called

cytokines) that alert the troops if there's a problem--the cellular

equivalent of dialing 9-1-1. But if too many of them are secreted,

people can get seriously ill. And if too few are secreted, the body

might not respond to an infection until it's too late.

Immunocompromised conditions

Immunocompromised individuals typically have at least one immune

system component missing. They can either inherit or acquire these

defects. For example, defects in a single gene can lead to two

inherited immunodeficiency disorders that involve B cells. (See

" Defective Gene Linked to Two Inherited Immune Deficiencies. " ) These

disorders predispose individuals to severe infections in the

respiratory, sinus, and gastrointestinal systems. Many

immunocompromised conditions, however, are acquired.

As for acquiring such defects, in 2006, UNAIDS and the World Health

Organization estimated that approximately 39.5 milling people were

living with HIV. That year alone, there were 4.3 million new

infections, with the majority occurring in sub-Saharan Africa. HIV

targets T cells, and in particular, T helper cells, which are critical

to fighting infections caused by fungi and parasites. This is why

people with advanced, untreated AIDS develop unusual infections such

as Pneumocystis carinii pneumonia and Toxoplasmosis gondii. AIDS is

the diagnostic term given to people with these life-threatening

infections.

(Note: Pregnant women also have varying levels of

immunodeficiency--otherwise they would reject the fetus, a foreign

body--and are susceptible to acquiring infections such as

Toxoplasmosis gondii. Therefore, they shouldn't clean cat litter

boxes, where these parasites abound.)

Since transplanted organs such as kidneys, hearts, livers, and lungs

are foreign bodies, recipients' immune systems must be permanently

suppressed to prevent them from attacking and destroying the organs.

More than 19,000 transplants are performed in the United States each

year. Each month, approximately 3,700 people are added to the U.S.

national transplant waiting list, and each day, 77 people receive

organ transplants. The breakthrough in transplant technology occurred

in 1983 when cyclosporine, a powerful immunosuppressive drug, became

licensed. However, even with cyclosporine, transplanted organs

typically only last around 10 years before needing to be replaced.

Research efforts to induce bodies to tolerate transplanted organs

without using immunosuppressive drugs are ongoing. But until a

breakthrough in understanding immunologic tolerance or a way to grow

replacement organs occurs, newly immunocompromised organ-transplant

recipients will occur each year.

In addition, cancer chemotherapies typically causes immunosuppression.

Since cancer cells are cells that multiply uncontrollably, the goal of

cancer therapy is to kill them without killing too many normal cells.

Unfortunately, the cells involved in immunity are frequently adversely

affected by chemotherapy, thus rendering the patient vulnerable to

infections.

Autoimmune disorders are typically treated with immunosuppressive

drugs such as corticosteroids, 6-mercaptopurine, and azathioprine to

keep the immune system from attacking the body. For example, Crohn's

disease is an autoimmune disease in which the immune system attacks

the body's gastrointestinal system, causing intense pain, bleeding,

and obstructions. Another treatment is Infliximab, which stops the

body's inflammatory response. But these treatments only alleviate pain

and suffering, they don't cure the underlying immune disorder.

Challenges during pandemics

During the global 1918 influenza pandemic, millions of people died.

None of them were living with HIV/AIDS, possessed a transplanted

organ, or taking chronic immunosuppressive drugs. In planning for

future pandemics, vulnerable populations with these diseases must be

taken into account. They are at high risk for getting infections and

spreading them to others. Mathematical models of infectious disease

outbreaks that don't consider the increased susceptibility and disease

transmission risk of immunocompromised populations could underestimate

the speed of transmission and the outbreak's severity--depending upon

the characteristics of the populations in question. (See " Modeling the

Worldwide Spread of Pandemic Influenza: Baseline Case and Containment

Interventions, " " Containing Pandemic Influenza at the Source, " and

" Strategies for Mitigating an Influenza Pandemic. " ) Populations with

high percentages of immunocompromised individuals potentially could

have a more rapidly spreading outbreak than other areas with less

immunocompromised individuals. These communities would want to make

special plans to protect them--especially if they weren't eligible to

receive a vaccine in which the risks outweighed the benefits.

There should be a global priority to reduce the number of

immunocompromised populations. Some programs (preventing HIV

transmission and providing primary care) already exist, but they're

underfunded and receive little support. If they don't receive more

funding and support, the number of immunocompromised individuals will

continue to grow, which, in turn, will likely inadvertently fan the

flames of any spreading pandemic.

http://www.thebulletin.org/columns/laura-kahn/20080107.html