The growing number of immunocompromised

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”) 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 both B and T cells to recognize specific deadly invaders such as the smallpox, polio, and measles viruses. B cells need to see these pathogens enough times to remember that when they encounter them, they’re ready to launch their antibody 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.