Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of the immune system first described by NIH scientists in the mid-1990s that affects both children and adults. In ALPS, unusually high numbers of white blood cells called lymphocytes accumulate in the lymph nodes, liver, and spleen and can lead to enlargement of these organs. ALPS can also cause anemia (low level of red blood cells), thrombocytopenia (low level of platelets), and neutropenia (low level of neutrophils, the most common type of white blood cell in humans). These problems can increase the risk of infection and hemorrhage.

Why Is the Study of Autoimmune Lymphoproliferative Syndrome (ALPS) a Priority for NIAID?

ALPS can cause debilitating symptoms and put those affected at an increased risk for developing serious health conditions, including autoimmune diseases and lymphoma. Researchers at NIAID are working to develop safe and effective treatments targeting the genetic defects in people with ALPS and related disorders.

How Is NIAID Addressing This Critical Topic?

Researchers at NIAID focus on gaining a better understanding of the clinical and genetic characteristics of people with ALPS and related disorders. By identifying the genes responsible for ALPS symptoms, NIAID researchers not only help affected families but also increase understanding of how the immune system works.

Primary immune deficiency diseases (PIDDs) are rare, genetic disorders that impair the immune system. Without a functional immune response, people with PIDDs may be subject to chronic, debilitating infections, such as Epstein-Barr virus (EBV), which can increase the risk of developing cancer. Some PIDDs can be fatal. PIDDs may be diagnosed in infancy, childhood, or adulthood, depending on disease severity.

There are more than 200 different forms of primary immune deficiency diseases (PIDDs) affecting approximately 500,000 people in the United States. These rare genetic diseases may be chronic, debilitating, and costly. Read more about some of the individual PIDDs that NIAID is currently studying.

Since the 1970s, NIAID-supported investigators have been examining the causes and complications of PIDDs to improve the lives of patients and families. NIAID aims to improve diagnosis, explore new treatments and preventions for PIDDs, and facilitate genetic counseling. NIAID is home to the Primary Immune Deficiency Clinic, which provides diagnoses and disease management recommendations to patients and families whose lives are touched by PIDDs.

An estimated 8% of the U.S. population has an autoimmune disease. In this family of disorders, the immune system mistakenly attacks healthy, working parts of the body, damaging them as a result. Researchers believe there are between 80 and 150 autoimmune diseases. Many of them are chronic and often debilitating, with no known cures. Treatments exist for just some of these diseases and don’t work for everyone. 

The immune system is designed to respond to pathogens and other threats like cancer with a built-in safeguard to avoid autoimmunity. Even so, the immune system can malfunction in ways that lead to autoimmune disease. NIAID-supported research seeks to understand how the immune system contributes to autoimmunity, to develop better diagnostic tools and animal models of autoimmune disease, and to identify effective treatment and prevention strategies. Unlike disease-specific research, this research approach has the potential to improve understanding and lead to treatments for many different autoimmune diseases.

NIAID-supported research has led to the identification of specific immune cells and molecular pathways involved in autoimmune disease, and consequently, to new treatment targets. This has contributed to an explosion in the number of therapies available, yet more work remains. Gaps persist in healthcare providers’ ability to match each person with the right therapy, in the availability of immune therapies that don’t increase the risk of infection, and in the existence of strategies to prevent and cure autoimmune diseases.

West Nile virus (WNV) is a member of the flavivirus family, which includes other mosquito-borne viruses such as dengue and Zika. WNV emerged for the first time in the Western Hemisphere in New York City in 1999 and has since spread across the United States. It is now the most common arthropod-borne virus found in the U.S. 

Most people (about 8 out of 10) who are infected with WNV develop no symptoms at all, while a smaller proportion develop mild symptoms of fever, body aches, skin rash, and swollen lymph nodes. If the virus crosses the blood-brain barrier, however, it can cause life-threatening conditions that include inflammation of the brain and spinal cord. There are no specific therapies for serious WNV infection and there is currently no vaccine available to prevent infection. 

NIAID supports research aimed at better understanding of the interactions between WNV virus, mosquitoes, and the human immune response, as well as broad-spectrum anti-flavivirus drug discovery efforts. 

Asthma is a chronic lung disease characterized by episodes of airway narrowing and obstruction, causing wheezing, coughing, chest tightness and shortness of breath.

Why Is the Study of Asthma a Priority for NIAID?

Asthma reduces quality of life and is a major contributing factor to missed time from school and work. Severe asthma attacks may require emergency room visits and hospitalizations, and they can be fatal. Existing asthma treatments focus on preventing or controlling disease symptoms. While treatment based on NIH guidelines is generally effective at improving asthma control, many people still experience symptoms on a regular basis and suffer from asthma attacks, which can be frightening and dangerous. NIAID and other NIH institutes studying asthma are committed to reducing the burden of this disease, which disproportionately affects minorities and families living at or below the poverty line.

How Is NIAID Addressing This Critical Topic?

NIAID supports targeted research to understand the underlying immune responses that lead to asthma. This understanding may aid the development of asthma prevention strategies and treatments to improve life for those already living with the disease. NIAID research focuses on understanding how environmental exposures interact with a person’s genetic makeup to cause immune responses that contribute to development of asthma or increase its severity.

Lyme disease, or borreliosis, is caused by the bacterium Borrelia burgdorferi and is transmitted to humans through the bite of an infected blacklegged deer tick. It is the most common tickborne infectious disease in the United States.  

State health departments reported 42,743 confirmed or probable cases to the Centers for Disease Control and Prevention (CDC) in 2017. Reported cases are not believed to reflect the actual incidence of Lyme disease, and CDC estimates that 300,000 cases likely occur annually. The incidence of Lyme disease, as with many other tick-borne diseases, has increased dramatically over the past 10 years.

Rocky Mountain spotted fever is a tickborne disease first recognized in 1896 in the Snake River Valley of Idaho. It was originally called “black measles” because of the look of its rash in the late stages of the illness, when the skin turns black. It was a dreaded, often fatal disease, affecting hundreds of people in Idaho. By the early 1900s, the disease could be found in Washington, Montana, California, Arizona, and New Mexico.

Tickborne diseases are becoming a serious problem in this country as people increasingly build homes in formerly uninhabited wilderness areas where ticks and their animal hosts live. Tickborne diseases can be caused by viruses, bacteria, or parasites. Most people become infected through tick bites during the spring and summer months.

Because of the work started by Dr. Ricketts in the early 1900s, NIAID Rocky Mountain Laboratories (RML) remains a thriving center for infectious disease research on tickborne diseases, such as Lyme disease and relapsing fever. RML also continues to do research on rickettsial diseases.

The incidence of tickborne infections in the United States has risen significantly within the past decade. Due to this increase, it is becoming more important that public health officials and scientists improve their understanding of pathogenesis, design improved diagnostics, and develop preventive vaccines for tickborne illnesses.

Tickborne diseases are becoming a serious problem in this country as people increasingly build homes in formerly uninhabited wilderness areas where ticks and their animal hosts live. Tickborne diseases can be caused by viruses, bacteria, or parasites. Most people become infected through tick bites during the spring and summer months.

Scientists are searching for better ways to diagnose, treat, and prevent tickborne diseases. They are also looking for ways to control the tick populations that transmit microbes.

Smallpox, caused by the variola virus, was a highly contagious infectious disease that caused infected individuals to develop a fever and a progressive, disfiguring skin rash. Three of out 10 individuals infected with smallpox died. Many survivors have permanent scars, often on their faces, or were left blind. Through vaccination, the disease was eradicated in 1980.  However, research for effective vaccines, drugs and diagnostics for smallpox continues in the event it is used as a bioterror weapon.

The last naturally occurring case of smallpox was reported in 1977. In 1980, the World Health Organization declared that smallpox had been eradicated. Currently, there is no evidence of naturally occurring smallpox transmission anywhere in the world. Although a worldwide immunization program eradicated smallpox disease decades ago, small quantities of smallpox virus officially still exist in two research laboratories in Atlanta, Georgia, and in Russia.

Why Is the Study of Smallpox a Priority for NIAID?

Smallpox is a category A pathogen which are those organisms/biological agents that pose the highest risk to national security and public health because they can be easily disseminated or transmitted from person to person, result in high mortality rates and have the potential for major public health impact, might cause public panic and social disruption, and require special action for public health preparedness.

How Is NIAID Addressing This Critical Topic?

NIAID supports basic, preclinical, and clinical research needed to advance product development for biodefense and emerging infectious diseases. Product development goals in this arena have shifted from a “one bug-one drug” approach to a more flexible strategy that is applicable to a broad spectrum of infectious diseases. Specifically, this broad-spectrum approach is being used to develop products effective against a variety of pathogens and toxins; find technologies that can be widely applied to improve multiple classes of products; and establish platforms that can reduce the time and cost of creating new products. This is evident in both the treatment and vaccine research NIAID has supported for smallpox, outlined below.

Shigellosis is an infectious, diarrheal disease caused by a group of bacteria called Shigella. Transmission of Shigella usually occurs through contact with the “4 Fs,” which are food, feces, flies, and fomites (inert surfaces). It also can also be spread through sexual contact. The disease typically resolves in 5 to 7 days. 

Why Is the Study of Shigellosis a Priority for NIAID?

Estimates on the number of shigellosis cases vary, as many mild cases often are not diagnosed or reported. Shigella cause an estimated 450,000 infections in the United States each year and an estimated $93 million in direct medical costs. 

How Is NIAID Addressing This Critical Topic?

NIAID supports basic research to study the bacterial pathogens that cause shigellosis. Researchers are also developing vaccines to prevent Shigella infections in humans and ways to combat the effects of Shiga toxin geared towards protecting the public from this diarrheal disease and towards improving the general public health.