Rare Disease Report


Rare Infectious Diseases

Even a minor outbreak of a severe infectious disease can instantly capture the public’s imagination and cause acute alarm. Mass contagion is such a common fear that popular culture reflects it strongly—an entire genre of film and television is devoted to the nightmare scenario in which a few intrepid researchers race against the clock to save the world from an uncontained pathogen.

In the real world, the spread of any new rare infection generates high media attention. The prominent coverage devoted to the recent cases of Middle East respiratory syndrome (MERS), subjecting more than 16,500 South Koreans to government-mandated quarantine, was no exception.

Neither was the Ebola virus outbreak of 2014, a West African-basedepidemic that caused 6466 deaths in Africa (4808 in Liberia alone) and resulted in a handful of cases on US soil, with 2 confirmed American deaths.

The Ebola numbers reflect an important point about the disproportionate impact of infectious diseases: many that are rare in the United States are not rare in other world regions. Dengue fever, for example, infects almost 400 million individuals annually, and is a leading cause of death in the tropics and subtropics; however, reported cases in the United States are extremely uncommon.

Similarly, although usually fewer than 10,000 US cases of tuberculosis occur annually, TB is the world’s most deadly infectious agent, affecting almost one-third of the global population.

High US vaccination rates coupled with extraordinary health, healthcare, food quality, sanitation, hygienic, and infection control standards serve to mitigate the substantial degree of danger posed by infectious disease in many other countries. Nonetheless, Americans have invested a substantial amount of time, energy, and capital in both public and private infectious disease research. A crowded pipeline of experimental anti-infectious disease treatments and vaccines are currently being investigated in laboratories around the nation.

Communicable infectious diseases are mainly transmitted by virus or bacterium. Viral diseases can be transmitted via various degrees of contact with animals (eg, chikungunya, hantavirus, Marburg hemorrhagic fever, rabies, yellow fever) or humans (eg, measles, Mollaret’s meningitis, poliomyelitis, rubella). Bacterial infections such as pertussis (whooping cough) can be transmitted from human to human, but this class of disease generally originates from human contact with infected animals or animal products (eg, anthrax, brucellosis, bubonic plague, typhus). Other rare sources of transmittable infection include fungi (eg, invasive aspergillosis, invasive mucormycosis) and parasites (eg, malaria, leishmaniasis).

Diagnosis Challenges

Accurate diagnosis of rare infectious disease is as important as it is tricky. Many diseases initially present with a symptom set that mimics more common, less urgent conditions. For the general population, the consequences of underdiagnosis or misdiagnosis include increased risk of spreading the infection. For patients, the direst consequence can be a delay that results in long-term complications or death. Some of these conditions attack so quickly that if they remain unidentified until symptomatic severity intensifies, they can be far more difficult— sometimes even impossible—to treat.

To be of optimum utility, diagnostic tools must be able to identify the infecting organism (or a surrogate marker thereof) in an accurate, simple, affordable, and, especially, fast manner. Results must also be processed in time to allow for effective control and containment measures to be instituted, such as quarantine, treatment, contact tracing, etc.

Online Resources

The FDA:
Centers for Disease Control and Prevention:

World Health Organization:

The Mayo Clinic:

Practice guidelines

Vaccination questions
www.cdc.gov/vaccines/hcp.htm, www.cdc.gov/vaccines/hcp/aciprecs/index.html

Orphan drugs approved by the FDA


Numerous infectious diseases, currently classified as rare, were once major killers. The widespread development and dissemination of vaccines to immunize children against the potentially debilitating, disfiguring, and/or deadly consequences of such diseases as measles and small pox, both that were formerly common and now reduced to the point of near extinction, represent a massive public health accomplishment whose importance cannot be overstated.

If no vaccination is available to prevent a given infectious disease, treatment modalities generally aim at eradicating their causes. For example, antibiotics are employed against bacterial infections, antivirals against viruses, anti-fungals against fungal infections, and antiparasitics against parasites.

Drugs most recently approved to treat orphan infectious disease include the following:

  • Isavuconazonium sulfate (Cresemba) for invasive aspergillosis and invasive mucormycosis: approved March 2015
  • Meningococcal Group B vaccine (Bexsero), a novel vaccine for invasive meningococcal disease: approved in January 2015
  • Miltefosine (Impavido) for leishmaniasis: approved March 2014

A sample of established treatments are:

  • Raxibacumab (Abthrax) and anthrax immune globulin (Anthrasil) for anthrax
  • Botulism antitoxin (BAT) for botulism
  • Alitretinoin (Panretin), daunorubicin (Cerubidine), interferon alfa-2a (Roferon-A), interferon alfa-2b (Intron A), paclitaxel (Taxol), and pazopanib (Votrient) for Kaposi sarcoma
  • Japanese encephalitis vaccine (Ixiaro) for Japanese encephalitis
  • Halofantrine (Halfan) melfloquine (Lariam), artesunate (Arinet), and quinine sulfate (Qualaquin) for malaria
  • Aminosalicylic acid (Paser granules), rifapentine (Priftin), rifampin (Rifadin), rifampin/isoniazid/pyrazinamide (Rifater), and bedaquiline (Sirturo) for tuberculosis

Clinical Trials

Below is a sampling of the robust and diverse slate of late-stage research initiatives currently underway in the realm of rare infectious disease. All of these diseases have agents being evaluated for their treatment in one or more phase 3 studies:

  • Chikungunya virus: chloroquine
  • Cystic fibrosis-related bacterial infection: tobramycin
  • Cytomegalovirus: ganciclovir, valganciclovir, artesunate, letermovir, maribavir
  • Ebola: amiodarone, V920 biological vaccine
  • Malaria: artemether-lumefantrine, dihydroartemisinin/ piperaquine, amodiaquine/sulfadoxine/pyrimethamine
  • Pertussis: immune globulin, vaccine
  • Tuberculosis: bedaquiline, pretomanid/linezolid, delamanid, mycobacterium vaccae, rifapentine, moxifloxacin, levofloxacin and isoniazid

Advocacy Support and Information

Rare disease advocacy groups provide essential support and represent a valuable repository of information, not only for patients but for clinicians. Key infectious disease advocacy groups include:

Immunization Action Coalition:



Pediatric Infectious Diseases Society:

The Immunization Partnership:

A more comprehensive listing appears in Appendix B of this resource guide.
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