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Report on the Rare Diseases Research Activities at the National Institutes of Health FY 2003

National Institute of Allergy and Infectious Diseases (NIAID)

Overview of Rare Diseases Research Activities

The National Institute of Allergy and Infectious Diseases supports research activities on rare diseases that are classified into four areas: infectious diseases, primary immunodeficiency diseases, autoimmune diseases, and other immune system-mediated conditions. Infectious diseases can be caused by viruses, bacteria, fungi, and other parasites. Primary immunodeficiency diseases are hereditary disorders caused by intrinsic defects in the cells of the immune system and are characterized by unusual susceptibility to infection. Autoimmune diseases result from a dysfunction of the immune system in which the body attacks its own organs, tissues and cells. NIAID research on rare diseases is aimed at delineating the mechanisms of disease pathogenesis and developing new and more effective strategies for the diagnosis, treatment, and prevention of these diseases.

Recent Scientific Advances in Rare Diseases Research

Rare Infectious Diseases

African Trypanosomiasis

African trypanosomiasis, also known as sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei, which is spread to humans through the bite of a tsetse fly and is almost always fatal if not treated. Only one new drug has been developed in the past 40 years, but it is toxic and has limited effectiveness. Thus, there is a critical need for new drugs. NIAID-supported scientists identified a trypanosome enzyme critical for DNA replication, which may provide a new target for the development of less toxic and more effective anti-trypanosomal drugs.


NIAID-supported scientists analyzed the full genome sequence of Bacillus anthracis, the bacteria that causes anthrax. Their analysis indicates that the regulation of gene activity, rather than the presence or absence of specific genes, plays an important role in the bacterium’s ability to cause severe disease and death. In addition, the researchers identified a number of genes encoding proteins that B. anthracis may use to enter host cells, which may be important targets for the development of vaccines and drugs.

The results of an NIAID intramural study of anthrax lethal toxin in mice suggested that anthrax lethal toxin induces circulatory shock and lethality differently from other bacterial toxins. Anthrax lethal toxin does not appear to act via excess release of inflammatory cytokines and nitric oxide, which are the targets for treatment of shock caused by other bacterial toxins. Therefore, anthrax induced shock may require alternate therapeutic strategies.


Blastomycosis is an infectious disease caused by inhaling spores of a fungus found in soil called Blastomyces dermatitidis. Serious fungal infections of immunocompromised people, including those with AIDS, are often due in part to low numbers of a type of immune cells called CD4+ T. Researchers studying mice with low CD4+ T-cell counts have discovered that vaccination against B. dermatitidis can increase survival from infection with this fungi. This finding demonstrates that fungal vaccines might help people with weakened immune systems fight disease-causing fungi by compensating for their low CD4+ T cell counts until those counts can return to normal.


NIAID-supported researchers used a genetic system to force the cholera bacterium Vibrio cholerae to express proteins in the laboratory that are only expressed within humans during disease. They found that several proteins involved in attaching cholera to the intestine surface were recognized by antibodies obtained from the blood of patients who were recovering from cholera. These results may inform the development of improved cholera vaccines and therapeutics. In addition, another group of NIAID-supported researchers determined the atomic structure of the V. cholerae pilus, which attaches the bacteria to the human gut. By studying the fine structure of the cholera pilus, the scientists gained insights in to the mechanism through which the pilus maintains its strength, flexibility, and multi-functionality.


Cryptococcosis, which is caused by the fungus Cryptococcus neoformans, is a life-threatening infection of the central nervous system that commonly affects immunocompromised individuals. Current antifungal drug treatments used to treat cryptococcus are toxic and frequently ineffective in eradicating central nervous system infection. Utilizing an animal model of C. neoformans infection, NIAID-supported scientists determined that the combination of antimicrobial drugs amphotericin B and fluconazole was more effective than currently used antifungal drug therapies. NIAID-supported scientists also discovered that when certain radioactive compounds were attached to monoclonal antibodies (mAB) which bind to the C. neoformans fungus, the radiation emitting mABs inhibited fungal growth in mice to a greater extent than unmodified mABs and did so without apparent toxicity. These results suggest radioimmunotherapy as a potential new treatment for fungal infections.


Cryptosporidiosis is an important cause of waterborne outbreaks of acute diarrhea, childhood diarrhea in developing countries, and AIDS-related diarrhea. In AIDS patients, the disease may cause a life-threatening chronic diarrheal illness that leads to wasting and death. NIAID-supported scientists have found that there is a positive correlation between the expression of a molecule called substance P and the severity of diarrhea in patients with cryptosporidiosis.

Cytomegalovirus(CMV) Disease

CMV is the virus most frequently transmitted to newborns during pregnancy. More than 90 percent of infants infected at birth who survive develop severe brain damage and/or profound hearing or visual problems. NIAID-supported scientists recently developed a guinea pig model that more closely mimics CMV infection in human newborns than the previously developed mice and rat models. This model system will be a valuable tool for gaining a better understanding of CMV infection in newborn human babies as well as evaluating potential new drugs or vaccines.

Two teams of NIAID-supported scientists have identified several host cell receptors that recognize CMV. The first team of NIAID-supported scientists demonstrated that the host cell receptors Toll-like receptor 2 and CD14 recognize CMV. The binding of CMV to these receptors triggers the production of inflammatory cytokines, which are immune system signaling proteins. Since many of the pathological processes associated with CMV disease are facilitated or directly mediated by inflammatory cytokines, identification of these cell receptors may ultimately lead to improved therapeutics. A second team of NIAID-supported scientists has identified another CMV cell surface receptor called epidermal growth factor receptor that is necessary for CMV entry into a host cell.


NIAID researchers have developed a live, weakened candidate vaccine against dengue virus, which is carried by mosquitoes and causes millions of cases of dengue fever each year. The virus also causes dengue hemorrhagic fever, which is lethal approximately 5 percent of the time. The experimental vaccine is chimeric, meaning that the structural genes from one type of dengue virus have been replaced with those of another type. NIAID is also supporting human clinical trials of a candidate Yellow Fever/dengue chimeric vaccine.

Escherichia coli (diarrheagenic)

Harmless strains of E. coli can be found widely in nature, including the intestinal tracts of humans and warm-blooded animals. Disease-causing strains, however, are a frequent cause of both intestinal and urinary-genital tract infections. E. coli and other bacteria communicate with one another using a system called quorum sensing, which is mediated by bacterial compounds called autoinducers. NIAID-supported scientists have identified a new autoinducer, AI-3, which is similar to the human hormones epinephrine and norephinephrine. The researchers speculate that the bacteria recognize AI-3 and epinephrine via the same bacterial receptor and that pathogenic E. coli use this receptor to "listen" to the hormonal communication of the host.

E. coli infections, as well as other microbial infections, are increasingly difficult to treat because of the emergence of drug-resistance strains. Multidrug efflux pumps, which are bacterial cell membrane structures, render antimicrobial drugs ineffective by pumping specific drugs out of the cell. The E. coli multidrug efflux pump AcrB pumps out the widest range of drugs, including penicillin, tetracycline, chloramphenicol, and streptomycin. NIAID-supported researchers used a novel technology to show that drugs are taken up from the thin space between the two outer membrane layers by a certain region of the AcrB efflux pump, and that this region seems to determine which drugs will be removed by the pump. Their analysis of clinical strains of drug-resistant bacteria showed that overproduction of these pumps is partially responsible for currently prevalent resistant bacteria.


Ebola virus is a rare and deadly microbe that causes hemorrhagic fever, characterized by high fever and massive internal bleeding. NIAID researchers have developed a fast-acting candidate Ebola vaccine that protects monkeys from the virus within one month following immunization. If this vaccine proves similarly effective in humans, it could one day be used to quickly contain Ebola outbreaks with ring vaccination—the same strategy used in the past against smallpox. Additionally, NIAID scientists have developed a human monoclonal antibody that neutralizes Ebola and protects guinea pigs from a lethal challenge with Ebola. These research results indicate it is possible to generate antibodies in cell culture that may be useful for passive immunization against Ebola virus infection.

NIAID researchers have also discovered that only three viral proteins are required for capsid assembly, a key life-cycle stage that renders Ebola infectious. In addition, they found that the sugar molecules that coat one of the capsid proteins are essential for virus formation. These findings could lead to the development of antiviral drugs for Ebola hemorrhagic fever.


Histoplasmosis is an infectious disease caused by inhaling spores of a fungus called Histoplasma capsulatum. Severe fungal infections in immunocompromised people, such as those with AIDS, are due in part to the low number of a type of immune cell called CD4+ T, which are needed to fight invading microbes. Researchers studying mice with low CD4+ T-cell counts have discovered that vaccines can increase survival from infection with H. capsulatum. When the researchers vaccinated mice against this fungus, another kind of T cell, called CD8+, helped overcome the lack of CD4+ T cells and enabled the mice to rid themselves of fungal infections.

Hepatitis E (HEV)

HEV is one of the most important causes of acute clinical hepatitis among adults in southeast and central Asia, the Middle East and North Africa. HEV also poses a risk to those who travel to areas where HEV is endemic, including military personnel. NIAID scientists have developed a HEV vaccine that is highly effective in preventing HEV in a nonhuman primate model of the disease. In addition, they found that the vaccine protected against several different strains of HEV, thus suggesting that a single vaccine may protect against HEV strains found worldwide.


Leishmaniasis is caused by infection with the Leishmania protozoa, which is transmitted by sand flies. In mammalian hosts, the parasites invade host macrophages, the cells responsible for destroying invading pathogens, and are able to persist even after patients recover from the active disease. NIAID investigators, studying mice resistant to Leishmania reinfection, discovered that the persistence of Leishmania in the skin following healing is controlled by a type of immune cell called CD4+CD25+ regulatory T cells. During the course of the infection, CD4+CD25+T cells were shown to accumulate at the site of infection and to inhibit the elimination of the parasite by the immune system. Paradoxically, when the activity of the CD4+CD25+ cells was inhibited, the parasite was eliminated, but the mice lost their immunity to re-infection.

Using a mouse model, NIAID-supported investigators sought to determine which parasite components are responsible for the parasite’s persistence after active disease is under control. They injected the mice with parasites that lack a particular Leishmania surface factor called lpg2. Parasites lacking this factor do not cause illness in the animals, but they do persist in the macrophages. Leishmania deficient in lpg2 may prove to be useful as vaccine candidates, since they have been shown to induce and maintain host immunity. In another study, NIAID researchers and their colleagues have developed a method to improve the safety of a Leishmania vaccine. Working with mice and monkey models, they found that injecting short pieces of DNA called CpG oligodeoxynucleotides at the time and site of vaccination with the live Leishmania vaccine improved the safety of the currently used vaccine while maintaining its effectiveness.

Lyme Disease

NIAID scientists detected Borrelia burgdorferi, the causative agent of Lyme disease, in mice nine months after treatment with therapeutic doses of antibiotics, though the remaining B. burgdorferi bacteria could not be transmitted to healthy mice. These results show that noninfectious B. burgdorferi can persist in mice for an extended period of time after antibiotic treatment, but the lingering bacteria are not associated with disease.

NIAID-supported scientists conducted a clinical trial to examine the effectiveness of antimicrobial therapy in reducing symptoms of patients with Lyme disease who have persistent severe fatigue at least six or more months after initial antibiotic therapy. The results indicated that additional antibiotic therapy in patients with post Lyme disease syndrome with severe fatigue resulted in an improvement in fatigue, but not an improvement in cognitive function or an experimental laboratory measure of infection.

All current blood tests using cultured Borrelia burgdorferi as their antigen source have been rendered obsolete by the widespread use of the recombinant OspA (rOspA) Lyme disease vaccine, LYMErix®. To address this problem, NIAID-supported scientists have developed a new assay to detect the Lyme disease pathogen, which can differentiate between naturally infected individuals and individuals vaccinated with the OspA LYMErix® vaccine. The genome of the B. burgdorferi has been sequenced and thousands of potential genes identified. During its life cycle, B. burgdorferi exists in distinctly different host environments, cycling between a tick vector and a mammalian host and therefore must regulate the activity of different genes depending on its current environmental conditions. Temperature is one environmental factor known to affect which genes are switched on and off. NIAID scientists have identified 215 genes that are differently expressed between 23ºC and 35º. Interestingly, 63 percent of the differently expressed genes lie outside the chromosome on a form of DNA called plasmids, which can be exchanged between individual bacteria.

Lymphatic Filariasis

Lymphatic filariasis, also known as elephantiasis, is best known from dramatic photos of people with grossly enlarged or swollen arms and legs. The disease is caused by parasitic worms, including Wuchereria bancrofti, Brugia malayi, and Brugia timori, and is transmitted by mosquitoes. NIAID-supported scientists at Case Western Reserve University, in collaboration with scientists in Papua New Guinea (PNG), studied the transmission rates of lymphatic filariasis before and after administration of the drug diethylcarbamazine. The scientists found that mass treatment of the population reduced the reservoir of the parasite to such a degree that transmission to humans by mosquitoes was dramatically reduced. Overall, the incidence of infection dropped by 86 percent. In addition, the treatments reduced clinical symptoms. The results of this study suggest that mass treatment with diethylcarbamazine can virtually eliminate the parasite reservoir and greatly reduce infection and clinical symptoms of lymphatic filariasis.


Microsporidiosis is caused by parasitic organisms of the phylum Microspora. The majority of cases of microsporidiosis involve diarrhea, but these parasites also cause respiratory, renal, and eye disease in immunocompromised people, such as those with AIDS. Microsporidia have a polar tube, which is a unique component of the organism used for invasion of the host. NIAID-supported scientists have identified modifications of polar tube proteins that may help explain how the organism interacts with the host cell. Interference with this mechanism may be a useful strategy to prevent infection.

Mycobacterium Avium Complex

Mycobacterium Avium complex disease is caused by a common bacterium found in water, soil, dust, and food. Prior to the introduction of highly active antiretroviral therapy (HAART) for the treatment of HIV/AIDS, disseminated infection with Mycobacterium avium complex (DMAC) was a common life threatening infection in HIV-infected patients. The standard of care for HIV-infected patients with DMAC was lifelong treatment with antibiotics because relapses of DMAC were common. In a recent study, NIAID-supported scientists showed that the withdrawal of preventative therapy could be safely accomplished in HIV-infected patients receiving HAART who been previously diagnosed with DMAC. This study demonstrated that the immune system of patients on HAART had been restored to a level sufficient for protection from a recurrence of DMAC.


Pertussis (whooping cough) is a preventable cause of cough illness in all age groups, but is rarely considered or diagnosed in older children or adults. NIAID scientists recently completed an adult efficacy trial of an acellular pertussis vaccine (a vaccine composed of bacterial fragments rather than whole bacteria). The results indicate that the vaccination of adults with the acellular pertussis vaccine provides protection for a finite period of time and boosters should be considered every 5 to 10 years.


Plague is caused by the bacterium Yersinia pestis, which is transmitted to people mainly through the bite of a flea. People with pneumonic lung plague can spread the bacterium directly to others. NIAID-supported researchers have identified a membrane protein that contributes to the ability of Y. pestis to evade the immune system. Identification of the role of this molecule may advance the development of novel therapeutic approaches for the treatment of plague.

Pneumocystis Pneumonia

Although the frequency of Pneumocystis carinii pneumonia (PCP) has decreased in the past decade, it continues to be one of the most common AIDS-defining illnesses. PCP is usually diagnosed by histological identification of the organism or by clinical assessment. NIAID-supported scientists have developed a new method for rapid diagnosis of PCP by measuring concentrations of the metabolite S-adenosylmethionine (S-AdoMet) in blood. This metabolite is essential for the pathogen’s survival, but during infection it is depleted. The detection method developed reveals that individuals with confirmed PCP have undetectable plasma concentration of S-AdoMet; those with no PCP have adequate plasma concentrations of S-AdoMet.


NIAID-funded scientists have sequenced the complete genome of the bacterium that causes Q-fever, Coxiella brunetti, which can cause a debilitating, though rarely fatal, flu-like illness in humans. The researchers have identified genes involved in cell entry, growth, and replication of the bacterium, and the mechanisms it uses to evade host defenses. This information may lead to new targets for vaccines, therapies, and diagnostics against Q-fever and other intracellular bacterial infections.

Severe Acute Respiratory Syndrome (SARS)

NIAID-supported investigators were the first to report to the World Health Organization the isolation of a virus that was conclusively linked to SARS patients. In addition, NIAID-supported scientists also discovered that the live animal markets in China may have been the origin of SARS transmission to humans. The researchers collected specimens from more than 25 animals in a live animal retail market in Shenzhen. Genetic tests on the samples confirmed that two animal species, the Himalayan palm civet and the raccoon-dog, were positive for a virus nearly identical to the virus that causes SARS.

NIAID scientists have discovered that the SARS virus replicates in the respiratory tract of mice and African Green monkeys to levels that will permit an evaluation of the efficacy of vaccines, immunotherapeutic, and antiviral drug treatment strategies. The researchers, using the mouse model, observed that primary infection with the SARS virus provides protection from re-infection and that antibody alone can protect against viral replication. These results suggest that vaccines which induce neutralizing antibodies, strategies for immunoprophylaxis, and immunotherapy may be effective in SARS.


Schistosomiasis is caused by parasitic worms. NIAID investigators have demonstrated that IL-13, the immune system regulatory molecule that is the primary stimulus for liver fibrosis in schistosomiasis-infected individuals, induces expression of a similar decoy molecule that acts as a potent inhibitor of tissue scarring. When mice are deficient in the decoy receptor, liver disease caused by schistosome infection is exacerbated significantly. Nevertheless, when the receptor deficient animals are treated with a soluble form of the receptor, disease is ameliorated.


NIAID researchers have developed a rapid and sensitive test for measuring antibodies to vaccinia virus, a virus similar to the smallpox virus, which can neutralize the smallpox virus. In addition, NIAID-supported investigators have identified molecular regions (peptides) of two different proteins that are common to the smallpox virus and the related vaccinia virus and have shown how the human immune system recognizes these peptides. These findings indicate how vaccination with vaccinia may provide immunity to smallpox and also could pave the way to the development of safer smallpox vaccines.

Streptococcal Group A Invasive Disease

The vast majority of infections caused by the common bacterium Group A Streptococcus (GAS) are noninvasive and milder than the more severe invasive form of the disease, which is relatively rare in the United States. It is difficult to treat invasive GAS disease, which is associated with high morbidity and mortality. By examining the interaction between disease-fighting cells called white blood cells and a strain of GAS that causes abundant disease in North America and Western Europe, NIAID scientists have discovered how this bacteria elicits its protective response to evade destruction by the human immune system. The scientists found that GAS becomes more resilient to attack by the host immune system over time, and that this resiliency is demonstrated by the increased expression of various GAS genes associated with the bacteria’s virulence and cell wall repair as well as genes that encode proteins likely to promote immune evasion.

Streptoccus Group B

Group B streptococcus (GBS) is a type of bacteria that causes illness in newborn babies, pregnant women, the elderly, and adults with other illnesses. GBS remains a leading cause of serious neonatal infection, despite the reduction in early-onset GBS disease in infants by the administration of antibiotics at the time of delivery. Immunization offers advantages over the use of antibiotics since it is less invasive, does not need to be administered during each pregnancy, is cost effective, and has the potential to prevent early- and late-onset GBS disease. NIAID scientists conducted a phase 1 clinical trial in pregnant women to determine the safety and immunogenicity of a GBS vaccine. They found that the vaccine was well tolerated and that there was excellent transfer of GBS-specific antibodies across the placenta to infants. Maternal immunization with this GBS vaccine may prevent GBS disease in pregnant women, neonates, and young infants.

Streptococcus Pnemoniae, Drug Resistant Invasive Disease

Streptococcus pneumoniae causes thousands of cases of meningitis and pneumonia in the United States each year. Currently, about 30 percent of S. pneumoniae isolates are resistant to penicillin, the primary drug used to treat this infection. Many penicillin-resistant strains are also resistant to other antimicrobial drugs. NIAID scientists had previously identified a set of genes that play a critical role in the expression of penicillin resistance in pneumococci. They have recently discovered three important functions of these genes: (i) they are essential for the biosynthesis of components of the bacterial cell wall; (ii) they are essential for the expression of penicillin resistance; (iii) and, when inactivated, they make the bacteria hypersensitive to the action of several antibiotics.


Infection with the common protozoan parasite Toxoplasma gondii causes a range of symptoms from asymptomatic chronic illness to mental retardation, retinal disease, and fatal brain infection. It is particularly threatening to developing fetuses and to immunocompromised individuals. To aid in the diagnosis and treatment of toxoplasmosis, NIAID researchers have developed an assay that distinguishes between virulent and non-virulent strains of T. gondii parasites. In addition, NIAID researchers have discovered that today’s predominant strains of Toxoplasma gondii gained the ability to infect nearly all warm-blooded vertebrates about 10,000 years ago through a genetic cross. This study established that parasites like T. gondii can sometimes rapidly adapt to new hosts and present potential new public health threats.

NIAID-supported scientists characterized the primary structure of a gene for an enzyme essential for T. gondii replication and virulence. Understanding the structural and functional differences between the human and parasite enzymes may lead to the discovery of a drug that inhibits the parasite enzyme but not the human one.

Transmissible Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases such as scrapie of sheep, Creutzfeldt-Jakob disease (CJD) of humans, bovine spongiform encephalopathy ("mad cow" disease), and chronic wasting disease (CWD) of deer and elk. TSEs are caused by accumulation of prion protein, an abnormal form of a protein found in humans and animals. Recently, NIAID scientists established that the TSE disease hamster scrapie can cause subclinical disease and jump species, adapting to and causing disease in mice. NIAID scientists have also demonstrated that cells used in some vaccine applications can be easily infected with TSE agents.

To expedite the identification of more effective TSE drugs, NIAID investigators have developed a high throughput screen for inhibitors of TSE prion protein accumulation. Using this assay, the investigators screened over 2000 FDA-approved drugs and natural products, 310 of which inhibited the accumulation of the abnormal prion form associated with scrapie in cells grown in culture.


Tularemia (also known as deerfly fever or rabbit fever) is an infectious disease caused by the bacterium Francisella tularensis. It is naturally found in small mammals such as rabbits, rodents, and hares, as well as the insects that feed on these animals. NIAID-supported scientists studying mice infected with F. tularensis have discovered that the immune cells and signaling molecules necessary to combat the early stages of systemic tularemia do not appear to combat early pulmonary tularemia. This finding suggests that the effectiveness of particular antibacterial host defenses varies depending on the invasion site.

West Nile Virus (WNV)

NIAID-supported scientists have developed a novel immunoassay that can differentiate WNV infection from other similar flavivirus infection. The newly-developed assay, which targets a WNV protein not found in other flaviviruses substantially improves the specificity of the assay and decreases the frequency of false positive results.

NIAID scientists have created a promising vaccine against WNV by replacing parts of a distantly related virus known as dengue type 4 with the corresponding proteins from the WNV. The researchers found that the resultant hybrid virus vaccine protected monkeys from West Nile infection. To ensure the safety of this vaccine in humans, the scientists further weakened the West Nile/dengue 4 virus by deleting some of the genetic material from the dengue virus.

Rare Primary Immunodeficiency Diseases

Chronic Granulomatous Disease (CGD)

CGD is an inherited genetic disorder characterized by failure of white blood cells (neutrophils, which are a type of immune cell) to produce the hydrogen peroxide needed to kill microorganisms, thus resulting in an increased susceptibility to bacterial and fungal infections. The results from a ten-year clinical trial of patients with CGD conducted by NIAID scientists indicate that the addition of the anti-fungal agent itraconazole to the routine medicines used in the management of CGD can significantly reduce the occurrence of fungal infections in these patients. In addition, NIAID scientists developed an animal model to study gene therapy or blood cell transplantation therapy in patients with CGD and other inherited diseases of the immune system. They transferred human blood stem cells from patients with CGD into a mouse strain that accepts human cell transplants to generate mice with the CGD phenotype (failure to produce hydrogen peroxide). When a functional copy of the CGD gene was inserted into CGD patient blood stem cells before they were transferred into mice, the resultant mice did not have the CGD phenotype.

DiGeorge Syndrome

DiGeorge syndrome is a congenital primary immunodeficiency disorder in which the thymus gland, heart, and parathyroid glands fail to develop normally. People with complete DiGeorge syndrome have no thymus, the organ located in the upper chest cavity. The thymus is required for the normal development of T lymphocytes, which are a type of immune cell crucial for protection against certain bacterial and viral infections. Complete DiGeorge syndrome is 100 percent fatal by three years of age. NIAID-supported researchers found that the transplantation of thymus tissue into patients with complete DiGeorge resulted in substantially enhanced survival and in partial restoration of immune function.

Wiskott-Aldrich Syndrome (WAS)

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the gene encoding the WAS protein (WASP). WASP plays an important role in signaling by T lymphocytes, a key component of immune system. WAS is characterized by a decreased ability to destroy infectious pathogens, which results in severe, recurrent, and/or life-threatening infections in affected individuals. Working with mice lacking a functional WASP gene, NIAID-supported scientists found that the WAS-associated immune cell signaling defects in these mice could be improved through the transplantation of blood stem cells containing the normal WASP gene.

Other Rare Immune-Mediated Conditions

Autoimmune Lymphoproliferative Syndrome (ALPS) and Related Disorders

ALPS is a disease affecting children which leads to the production of an abnormal number of specialized immune cells called lymphocytes, thus resulting in swollen lymph glands and organs and an autoimmune attack on the patient’s own tissues. Through the study of an ALPS-like genetic condition known to exist in only two individuals, NIAID scientists discovered that an enzyme called caspase-8, which is known to help trigger apoptosis (programmed death of cells) is also involved in activating many immune system cells needed to fight infections. This information may provide important insights into the pathogenesis and treatment of ALPS and related disorders, as well as more common autoimmune diseases such as diabetes, rheumatoid arthritis, and multiple sclerosis.

Systemic Lupus Erythematosus (SLE)

SLE is a serious, relapsing, systemic autoimmune disease, which is much more prevalent in women than in men. The disease is multisystemic, affecting a number of organs and tissues, including the joints, skin, kidneys, lungs, heart, and brain. NIAID scientists have developed an animal model for SLE using mice that do not make a protein that inhibits antibody production and inflammatory responses. These mice develop a spontaneous disease that resembles lupus in humans. Studies using this SLE animal model may provide insights that lead to the identification of therapeutic targets.

A NIAID-supported research team has shown that the female hormone prolactin can influence the development of cells that produce the type of antibodies responsible for symptoms of SLE. The treatment of mice susceptible to SLE with prolactin allowed the survival of antibody-producing cells that are normally eliminated by the immune system and led to the development of symptoms of SLE in the treated mice. The results may help explain why SLE is much more common in women than men.

In another study, NIAID-supported investigators measured the proteins encoded by over 12,000 genes and discovered that only 33 are elevated during periods of active lupus. These same genes are stimulated by interferon, an immune system signaling molecule, suggesting that the interferon pathway has a key role in SLE activity. These findings suggest that lupus has a relatively simple "signature" of gene activity, which may provide much-needed objective measures of disease activity (biomarkers), suggest approaches to treatment, and help to identify the causes of the disease.

New Activities

Rare Infectious Diseases

  • In FY 2003, NIAID issued a series of new RFAs and PAs that invited investigator-initiated research grant applications focusing on the development of new diagnostics, preventions, and treatments for toxins and pathogens listed in the NIAID categories A, B, and C list of priority pathogens, as well as the newly recognized SARS coronavirus. The newly issued initiatives included: Cooperative Research for the Development of Vaccines, Adjuvants, Therapeutics, Immunotherapeutics, and Diagnostics for Biodefense; Biodefense Partnerships: Vaccines, Adjuvants, Therapeutics, Diagnostics, and Resources; NIAID Investigator-initiated Small Research Grants; and Small Business Biodefense Program.

  • In FY 2003, NIAID announced two new programs, the Food and Waterborne Diseases Integrated Research Network and the Respiratory Pathogens Research Network. These programs expand NIAID’s capacity to conduct clinical research studies of food and waterborne pathogens, including those that could be potential agents of bioterrorism.

  • In FY 2003, NIAID issued the RFP In Vitro and Animal Models for Emerging Infections and Biodefense. This initiative aims to provide NIAID with a ready capability to test the efficacy of new vaccines and therapeutics for biodefense and emerging diseases. Tasks awarded in FY 2003 will use anthrax models to ultimately support FDA licensure applications for currently approved antibiotics determined to be efficacious for the treatment of inhalational anthrax.

  • In FY 2003, NIAID announced funding for the construction of two National Biocontainment Laboratories (NBLs) and nine Regional Biocontainment Laboratories (RBLs). The NBLs and RBLs will include state-of-the-art Biosafety level (BSL)-3 and BSL-4 laboratory facilities in which researchers can study potential agents of bioterrorism as well as naturally occurring infectious diseases in a safe, secure environment.

  • In FY 2003 NIAID funded eight Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) located throughout the country that will provide the scientific information and translational research capacity to make the next generation of therapeutics, vaccines, and diagnostics against the NIAID Category A-C Agents and emerging infectious diseases.

  • In FY 2003, NIAID issued the Small Research Grants for International Research in Infectious Diseases at NIAID International Sites. The aim of this initiative is to advance the development of local scientific expertise and to increase collaborative research partnerships at NIAID international sites.

    Rare Immune-System Mediated Diseases

  • NIAID, along with NICHD, established the Primary Immunodeficiency Diseases Consortium. The Consortium will: (l) provide leadership and mentoring; facilitate collaborations; enhance coordination of research efforts; and solicit, review, recommend, and make awards for pilot or small research projects; (2) maintain and expand a primary immunodeficiency diseases registry, which will provide data to the research community about the clinical characteristics and prevalence of these diseases; and (3) develop a repository of specimens from subjects with primary immunodeficiency diseases.

    Ongoing Activities

    Rare Infectious Diseases

    • In FY 2003, NIAID announced the expansion of the Vaccine Treatment and Evaluation Units (VTEUs) by approximately 60 percent. In the past year, eight clinical trials of various smallpox vaccines have been completed or are underway at VTEU sites. In addition, clinical trials for new anthrax and West Nile vaccines are being planned.

    • In FY 2003, NIAID expanded its support of a contract with Utah State University to conduct the evaluation of potential therapeutics for viral hemorrhagic fevers and encephalitides in animal models. In addition, NIAID scientists continue their work to develop a vaccine that would protect against multiple hemorrhagic fever viruses, including Ebola, Marburg, and possibly Lassa virus.

    • NIAID continues to collaborate with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) under an Inter-Agency Agreement to develop vaccine strategies for Ebola and other viral hemorrhagic fevers.

    • In FY 2003, NIAID and FDA, through an inter-agency agreement, supported the screening of compounds that may be effective against biodefense-related and emerging viruses (vaccinia, cowpox, West Nile, yellow fever, SARS, etc.).

    • In FY 2003, in response to the rapid need for expanded research activities on the basic biology and immunology of the SARS coronavirus, NIAID awarded supplements to grantees to: produce SARS virus proteins, generate diagnostic/therapeutic monoclonal antibodies, analyze mechanisms for SARS specific antibody neutralization, and animal model development; evaluate selected compounds that stimulate the innate immune system to treat SARS; initiate studies at the China CDC on the interactions between SARS, HIV, and TB; develop viral replication-based therapies to the SARS coronavirus, including protease inhibitors; and identify antibody inducing epitopes of SARS proteins that can be used for vaccine development.

    • NIAID is supporting the development of SARS coronavirus vaccines through a variety of grants and contracts. In FY 2003, NIAID awarded separate contracts to Aventis Pasteur and Baxter for the development of inactivated SARS coronavirus vaccines. NIAID also awarded a contract to Protein Sciences for the development of a recombinant SARS vaccine. In addition, NIAID initiated the development of three different SARS vaccine projects through a grant supplement to the China CDC and their collaborators. NIAID scientists are also developing a DNA-based SARS vaccine and a strategy to combine these various vaccine approaches with inactivated SARS coronavirus proteins to see if a combination vaccine is more immunogenic.

    • NIAID, in collaboration with USAMRIID and the CDC, is supporting the in vitro screening of candidate drugs against the SARS coronavirus. In addition, NIAID awarded two contracts for screening for antiviral drugs that can be used to treat SARS. One contract was awarded to Utah State University and the other was awarded to the Southern Research Institute at the University of Alabama at Birmingham. NIAID intramural scientists also began developing antiviral peptides that will block the SARS coronavirus from entering cells and might be useful as a therapeutic drug to treat or prevent SARS.

    • In FY 2003, NIAID provided funding through a contract to the Massachusetts Biologic Laboratories for the development of a type of antibody that can be used to treat people infected with SARS.

    • In FY 2003, NIAID has expanded its Pandemic Preparedness contract at St. Jude Children’s Hospital to: expand efforts to identify the animal reservoirs for coronaviruses in Asia; establish cell-based laboratory assays to assess the immune response in infected patients; and conduct studies of family members and other close contacts of SARS patients to assess the rates of asymptomatic infections.

    • In FY 2003, NIAID awarded two contracts to support pre-clinical and clinical studies to control selected human respiratory pathogens. The contract awarded to the University of Iowa will support research focused on bacterial respiratory pathogens. The second contract, awarded to the Baylor College of Medicine, will focus on viral pathogenesis and evaluation of new viral vaccines and therapeutics.

    • In FY 2003, NIAID provided initial support via a fast-track grant to Acambis, Inc. to develop a live, attenuated vaccine for WNV. Thus far, this vaccine has demonstrated good safety, efficacy, and protection against disease in animal models. NIAID intramural researchers are also working to develop another live, attenuated WNV vaccine.

    • In FY 2003, a phase I/II randomized, placebo-controlled clinical trial was initiated at 35 sites in the United States to assess the safety and tolerability and efficacy of intravenous immunoglobulin G (Omr-IgG-amTM) containing high anti-West Nile virus antibody titers in patients with or at risk for progression to WNV encephalitis and/or myelitis.

    • In FY 2003, NIAID converted a grant awarded to the University of Texas Medical Branch supporting the World Reference Center for Arboviruses into a contract entitled World Reference Center for Emerging Viruses and Arboviruses. The center provides scientists with basic and applied research resources on arboviruses (including WNV) and other emerging viruses and provides a forum to train investigators in virus identification and characterization techniques.

    • In FY 2003, NIAID issued the RFP, In Vitro Antiviral Screening Program. The goal of this initiative is to provide drug screening resources for researchers engaged in antiviral research and to promote the discovery and development of new therapeutics for medically important, emerging, and rare viral diseases.

    • In FY 2003, NIAID continued its support for the Collaborative Antiviral Study Group (CASG), which is a collaborative network, composed of 63 institutions, that conducts clinical studies of therapies for viral infections. Through the CASG, NIAID supports four pediatric clinical trials aimed at treating neonatal herpes simplex virus infections, sepsis caused by a group of viruses called enteroviruses, and CMV infections involving the central nervous system.

    • NIAID awarded a contract to the University of Alabama for a Respiratory Pathogens Reference Laboratory. This contract will provide a resource facility with a major effort on reagent and assay development for measurement of the human immune response to targeted bacterial respiratory pathogens.

    • NIAID continues to support Phase I/II trials for two different candidate vaccines for human cytomegalovirus. In one of the studies for which enrollment is ongoing, a vaccine against CMV is being evaluated in post-partum CMV-seronegative women for its ability to prevent infection in these women. In another study, four live recombinant viruses are being evaluated for safety in seropositive individuals. This vaccine was well-tolerated with no significant side effects in this population.

    • In FY 2003, NIAID continued its support of an ongoing phase III clinical trial conducted by the Adult AIDS Clinical Trials Group to determine whether the antiviral drug valganciclovir is safe and effective in preventing CMV organ damage in HIV-infected subjects.

    • NIAID has continued its support of the Bacteriology and Mycology Biostatistical and Operations Unit and the Bacteriology and Mycology Study Group initiatives, which support clinical trials against fungal and resistant bacterial infections.

    • NIAID continues to support research on the prevention of group B streptococcal disease through a contract awarded to researchers at Brigham and Women’s Hospital. This collaborative multidisciplinary effort is focused on clinical studies in selected populations to further understand GBS infection and on studies of the host immune response.

    • In FY 2003, NIAID supported several clinical trials of group B streptococcal vaccines. Researchers at Baylor College of Medicine are conducting a trial to evaluate the safety and immunogenicity of a booster dose of a group B streptococcal type vaccine in 50-64-year-old healthy adults. In addition, researchers at the Magee-Women’s Hospital are conducting a Phase II clinical trial of a group B streptococcal vaccine in 18-30 year old women to evaluate prevention of vaginal acquisition of GBS type III.

    • A RFA, Partnerships for Vaccines and Diagnostic Development, was announced in FY 2003, and awards will be made in FY 2004. This RFA focuses on the development of vaccines against Group A Streptococci (GAS), Group B Streptococci, and Helicobacter pylori.

    • For over 30 years, NIAID has supported two helminth (parasitic worm) resources that serve the research community. The Schistosome Resource Center is maintained by Biomedical Research Institute and the Filaria Resource Center is maintained by University of Georgia. Both contracts were renewed in FY 2003.

    • NIAID has continued to actively test new candidate compounds for efficacy against infectious complications of AIDS in culture and in animals through its anti-infective drug development contracts. These contracts have been awarded for research on several rare diseases caused by these microorganisms Mycobacterium avium, Pneumocystis, Cryptosporidium, Cryptococcus and Microsporidium.

    • In FY 2003, NIAID continued its support of research into the fundamental mechanisms of TSE disease and transmission as well as the development of diagnostic tests and effective therapies. NIAID awarded a contract to Colorado State University to establish an emerging disease research center focused on the TSE Chronic Wasting Disease (CWD), which will investigate the mechanics of CWD infection in deer and elk. In addition, NIAID-supported scientists are evaluating potential anti-TSE compounds in animal models. Through expansion of an NIAID contract with Utah State University, candidate compounds are evaluated for efficacy in animals.

    • In FY 2003, NIAID awarded a contract to TIGR to support a Microbial Genome Sequencing Center to allow for rapid and cost-efficient production of high-quality, microbial genome sequences. This center has the capacity to respond to national needs and Federal agencies’ priorities for genome sequencing by providing genome sequencing data for multiple usages, including forensic strain identification and the identification of targets for drugs, vaccines, and diagnostics.

    • In FY 2003, NIAID supported approximately 36 large scale DNA sequencing genome projects for microbial pathogens and invertebrate vectors of infectious diseases, including new projects for different strains and clinical isolates of Bacillus anthracis and another strain of Clostridium perfringens. Genome sequencing projects for the bacteria Burkholderia mallei, Clostridium perfringens, Escherichia coli (K1 RS218), Streptococcus agalactiae, Rickettsia rickettsii, Rickettsia typhi, Salmonella typhi, and Wolbachia were completed in FY 2003.

    • NIAID has continued its support for the Pathogen Functional Genomics Resource Center at The Institute for Genomic Research (TIGR). The center was established to provide and distribute to the broader research community a wide range of genomic and related resources and technologies for the functional analysis of microbial pathogens and invertebrate vectors of infectious diseases. In FY2003, additional organism-specific resources were generated and distributed to the scientific community, including SARS-related resources.

    • NIAID has continued to provide support for databases of genomic and post-genomic information and analysis tools on sexually transmitted pathogens and poxviruses. Genomic information for thirteen bacteria and viruses are now included in STDGEN, a database designed to accelerate research on sexually transmitted diseases. The Poxvirus Bioinformatics Resource Center is a web-based resource for scientists that facilitates basic research on poxviruses as well as research into new therapies and vaccines against them.

    • NIAID staff continues to participate in the Microbe Project Interagency Working Group, which previously developed a coordinated, interagency five-year action plan on microbial genomics. In FY 2003, the Microbe Project Interagency Working Group developed a document on the subject of data sharing of pre-publication DNA sequencing data.

    • NIAID has continued to participate in a coordinated Federal effort in biodefense genomics and is a major participant in the National Inter-Agency Genomics Sciences Coordinating Committee that includes many Federal agencies. In FY 2003, the committee focused on category A agents and provided the CDC with new technological approaches for sequencing additional smallpox viral strains.

    Immune-System Mediated Rare Diseases

    • NIAID continues to support demonstration and education research projects aimed at increasing minority involvement in organ donor registries. The Legacy Donor Registry in Louisiana endeavors to increase organ donation by using new and non-traditional approaches to organ donor recruitment, improving the consent process to enhance organ donations, and facilitating the medical community’s access to donor registry information.

    • NIAID continues to support The Minority Community Outreach on Organ Donation and Transplantation at the Hope Heart Institute in Seattle, WA. This community-based outreach network is dedicated to increasing organ donation among minority populations in Seattle and Tacoma, Washington. A second research project at the Hope Heart Institute is directed at increasing organ donation among rural Alaskan Natives. Culturally sensitive educational materials and community health education programs are being developed on transplant options, and living and cadaveric organ donation for this population.

    • In FY 2003, NIAID and NCRR made an award under the RFA National Swine Research and Resource Center to establish a facility for depositing, maintaining, preserving, and distributing swine research resources for studies of human diseases. Swine are a useful model for transplantation research because of their reproductive capacity, anatomical and physiological similarities to humans, and ability to be genetically modified.

    • NIAID awarded a multi-year, cooperative agreement entitled Systems Approaches to Innate Immunity, Inflammation and Sepsis to a multidisciplinary team of researchers at the Scripps Research institute. These researchers are employing a systems biology approach to create a comprehensive picture of innate immunity, an essential first line of defense against bacterial, viral, and fungal diseases.

    • NIAID, NIDDK, and ORWH continued to co-sponsor the Autoimmunity Centers of Excellence (ACEs), a cooperative program which supports collaborative basic and clinical research on autoimmune diseases, including single-site or multisite pilot clinical trials of immunomodulatory therapies. In FY 2003, this initiative was renewed and expanded to include 9 separate institutions. In addition, these Centers began enrolling participants in three trials.

    • The Autoimmune Disease Prevention Centers conduct basic research on the development of new targets and approaches to prevent autoimmune diseases and to evaluate these approaches in pilot and clinical studies. In FY 2003, the Prevention Centers supported 14 pilot projects to test innovative approaches, which may lead to the development of novel targets for disease prevention or assays for biomarkers of disease progression. The Prevention Centers are co-sponsored by NIAID, NIDDK, NICHD, ORWH, and Juvenile Diabetes Research Foundation International (JDRF).

    • Two new grants were awarded in FY 2003 under the Hyperaccelerated Awards for Mechanisms in Immunomodulation Trials RFA. This initiative supports immune-based mechanistic studies associated with clinical trials of infectious disease vaccines and immunotherapies for immune-mediated diseases. Applications are abbreviated, submitted and reviewed monthly, and awarded as early as 13 weeks after submission. This program is co-sponsored by NIAID and other NIH Institutes, Centers, and Offices.

    • NIAID supports the Immune Epitope Database and Analysis Program, which supports the development and maintenance of an integrated, web-based, searchable database of antibody binding sites (antibody epitopes) and antigenic MHC-binding peptides (T cell epitopes) for a wide variety of infectious agents and immune-mediated diseases. It is anticipated that the information contained within the database and the availability of analysis tools will facilitate identification of novel vaccine candidates and immunotherapeutic strategies.

    • NIAID, NIDDK, and JDRF co-sponsor the Immune Tolerance Network (ITN), an international consortium of scientists and clinicians dedicated to the clinical evaluation of promising tolerance induction therapies in four areas: autoimmune disorders, kidney transplantation, islet transplantation for type 1 diabetes, and asthma and allergic diseases. The network is also developing assays and biomarkers to measure the induction, maintenance, and loss of immune tolerance in humans and is studying underlying mechanisms as an integral part of all clinical trials. The ITN includes basic scientists and physicians at more than 40 institutions in the United States, Canada, and Europe.

    • NIAID supports the Multiple Autoimmune Diseases Genetics Consortium (MADGC), a repository of genetic and clinical data and specimens from families in which two or more individuals are affected by two or more distinct autoimmune diseases. This repository provides well-characterized material for use in research aimed at identifying the genes involved in autoimmune diseases. MADGC began enrolling families in May 2000 and aims to have 400 enrolled in 2004. To date, 162 families have been fully enrolled, and 125 families are in the process of being enrolled.

    • NIAID, in conjunction with NIAMS, NINDS, ORWH, and the National Multiple Sclerosis Society, continues to support the Sex Based Differences in the Immune Response research initiative. Differences in the immune response of males and females have been documented, including the increased incidence of autoimmune diseases in women. The cause of pregnancy-induced changes in immune mediated diseases and differences in the rate and severity of disease are unclear. An increased understanding of the mechanisms underlying the differences in the immune response in males and females should allow more targeted approaches for the prevention and treatment of immune-mediated disease.

    • Through the Stem Cell Transplantation for Autoimmune Diseases Consortium, NIAID is supporting clinical trials to assess the efficacy of hematopoietic stem cell transplantation to treat several severe autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and scleroderma. Trials involving patients with systemic lupus erythematosus and scleroderma are expected to begin in 2004.

    • NIAID chairs the NIH Autoimmune Diseases Coordinating Committee (ADCC). The ADCC was established in FY 1998, at the request of Congress, to increase collaboration and facilitate coordination of research among NIH Institutes and Centers, other federal agencies, and private groups interested in these diseases. The ADCC Autoimmune Diseases Research Plan, which was mandated in the Children’s Health Act of 2000 (P.L. 106-310), was presented to Congress in FY 2003.


    • NIAID and GenVec, Inc. negotiated a CRADA to develop a recombinant SARS vaccine.

    • NIAID and Vical, Inc. negotiated a CRADA to develop WNV DNA vaccines for use as prophylactic vaccines in human and veterinary applications.

    Rare Disease-Specific Conferences, Symposia, and Meetings

    • On October 22-23, 2002, NIAID convened the Blue Ribbon Panel on Bioterrorism and its Implications for Biomedical Research, focusing on CDC Category B and C agents. This group of experts from academia, industry, and government provided expert advice, which led to the development of The Counter-Bioterrorism Research Agenda of the National Institute of Allergy and Infectious Diseases (NIAID) for CDC Category B and C Agents.

    • In November, 2002, NIAID, in collaboration with the NIH Office of Rare Diseases, sponsored an international conference on the current status of vaccines against plague and tularemia. Experts from throughout the world participated in this conference, which also stimulated productive interactions between various groups of investigators.

    • NIAID and the NIH Clinical Center convened a meeting on November 20-21, 2002, to discuss therapeutic options for individuals who suffer from West Nile Meningoencephalitis. The meeting provided a forum for experts from government, academia, pharmaceutical industry, and private clinical practice to discuss the recent outbreaks in the United States, focusing on epidemiology, disease, and potential therapeutics, and included identification of gaps in current knowledge and recommendations for courses of action.

    • Along with other funding agencies, NIAID organized two meetings (February, 2003 and September 2003) to assess progress and future directions for the three trypanosomatid genome projects: Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. These three genomes are nearing completion and plans are being made for publication.

    • NIAID, in cooperation with NIEHS, NIAMS, the NIH Office of Rare Diseases, the NIH Office of Research on Women’s Health, the American Autoimmune Related Disease Association, and the U.S. Environmental Protection Agency, sponsored a workshop which was held on February 4-5, 2003, to discuss recent progress in and potential future directions for research related to environmental influences on autoimmunity and autoimmune diseases.

    • NIAID organized the Imaging Technology and Study of Immune Function workshop, which was held April 8-9, 2003, to discuss recent progress in programs funded under the RFA New Imaging Technologies for Autoimmune Diseases and to advise the NIAID on future directions and opportunities to utilize imaging technologies to advance the understanding of immune system function.

    • On April 23-24, 2003, NIAID and the NIH Office of Rare Diseases co-sponsored a conference on Humoral Rejection in Solid Organ Transplantation, in Bethesda, MD. The goal of this conference was to evaluate the state of the science in diagnosing and treating humoral rejection. Additional co-sponsors were The American Society of Transplantation, American Society of Transplant Surgeons, National Kidney Foundation, International Society of Heart and Lung Transplantation, American Society of Histocompatibility and Immunogenetics, and the Division of Transplantation at the DHHS Health Resources and Services Administration.

    • On April 30 - May 1, 2003, NIAID sponsored the Genomics of Transplantation workshop. An expert panel addressed the state-of-the-science in complex trait disease and transplantation genomics; identified gaps in knowledge; and advised NIAID on immediate and long-term research opportunities in transplantation genomics.

    • On May 30, 2003, NIAID convened an international meeting on SARS and its implications for the biomedical research community. Experts in coronavirus biology, vaccine and drug development, diagnostics, epidemiology, and clinical management were asked to develop a robust research agenda leading to the development of effective products to control this disease.

    • NIAID scientists participated in a joint meeting of the U.S.-Japan Cooperative Medical Sciences Program’s TB and Leprosy Panels, which was held in Newark, NJ, on July 21-22, 2003. The goal of the meeting was to foster an exchange of ideas and stimulate international collaborations among U.S., Japanese, and other Asian Pacific Rim mycobacterial researchers.

    • On September 14-15, 2003, NIAID co-sponsored a conference on pediatric organ transplantation. The goals of this conference were to: identify critical organ-specific areas of research facing the pediatric transplant population; identify obstacles to initiation of, participation in, and completion of clinical trials and develop strategies to overcome these obstacles; and develop concepts for organ-specific and all-organ research proposals that are feasible within the constraints of the study population. In the plenary sessions, participants discussed overviews of mechanistic studies in transplantation, existing registries, clinical study design, and the role of industry in clinical trials. Breakout sessions were devoted to establishing research priorities in thoracic, liver and small bowel, and kidney transplantation, as well as infectious diseases and mechanistic studies. Co-sponsors included the Office of Rare Diseases at the National Institutes of Health, the American Society of Transplant Surgeons, the American Society of Transplantation, the International Society of Heart and Lung Transplantation; the National Kidney Foundation; and the North American Pediatric Renal Transplant Cooperative Study.

    • On September 16, 2003, NIAID sponsored a conference on post-transplant lymphoproliferative disease (PTLD). The goals of this meeting were to: bring together experts in the field to enhance communication between transplant physicians, surgeons, oncologists, infectious disease specialists, pathologists, and basic scientists interested in PTLD; identify the priority areas for clinical trials and mechanistic studies in PTLD following solid organ transplantation; discuss how to overcome the problems of performing studies in heterogeneous patient populations involving a wide range of ages and solid organ transplants; and develop strategies for moving forward with multi-center studies of the priority areas identified by the conference participants. The multi-disciplinary group of experts addressed a range of topics, including: prevention of PTLD, biological and pharmacological therapies, and strategies to monitor and predict outcomes of therapy. This conference was co-sponsored by the National Cancer Institute and the Office of Rare Diseases at the National Institutes of Health.

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    Last Reviewed: January 27, 2005
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