Infectious diseases are the leading cause of death globally, accounting for one quarter to one third of the estimated deaths in 1998. Tuberculosis, HIV/AIDS, malaria and hepatitis continue to cause major morbidity and mortality in developing countries. Diarrhea diseases and measles both appear to have peaked at high incidence levels. Compounding the increasing threat of known infectious agents, previously unknown disease agents continue to be identified. At least 30 agents -including HIV, Ebola, hepatitis C, and Nipah viruses - have been confirmed since 1973; there is no known cure for subjects infected with one of these agents.

In the U.S., annual infectious disease-related death rates have nearly doubled to about 170,000 after reaching an historic low in 1980. Many infectious diseases originate outside the U.S. and the infectious agent is introduced through international travelers, immigrants, etc. The most dangerous infectious agents threatening the health of American citizens remain HIV/AIDS, hepatitis C, tuberculosis and influenza. Nosocomial infections in hospitalized patients and antibiotic-resistant organisms also cause significant morbidity and mortality.

Some infectious and immunologicl disease prevalence statistics are:

There are currently more than 200 drugs in clinical trials for conditions related to infections. The most active area is that of drugs for the treatment of HIV/AIDS infection. CenterWatch estimates that there are more than 80 drugs in development for HIV/AIDS and related complications. In the past ten years, major advances have been made toward decreasing mortality and morbidity from AIDS. However, the major disadvantage of the highly active antiretroviral therapy (HAART) is that the agents used are not virucidal and elimination of the virus cannot be achieved. Thus, when HAART treatment is stopped, viral loads return to pretreatment levels.

There is evidence that new forms of therapy may be necessary to combat viral resistance as well as to provide other options to life-long drug use. Such new therapies include:

In 2001, the FDA approved Valcyte (valganciclovir hydrochloride) tablets for CMV retinitis in patients with AIDS, Videx EC Capsules (a once daily formulation of didanosine), and Viread (tenofovir), the first nucleotide analog.

The past decade has seen the increased use of immunomodulators in infectious diseases. Some are already licensed for use (for example, granulocyte colony-stimulating factor G-CSF, interferons, and imiquimod), and others are being investigated in clinical trials (IL-12, CpG and other oligodeoxynucleotides, etc). Two new therapies in these areas were approved in 2001 for the management of chronic hepatitis C infection: Peg-Intron and Peg-intron/Rebetol. Peg-Intron is an injectable long-acting formulation of interferon-alpha 2b (Intron A), an antiviral/biological response modifier, and Rebetol is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity. Results of phase III trials showed that, when used together, Peg-Intron/Rebetol resulted in a 54% sustained virological response in previously untreated adults with chronic hepatitis C.

There are more than 40 drugs in clinical trials for various bacterial infections. Many of these are reformulations or compounds that are structurally similar to older antibiotics. The activity of existing antibiotics is decreasing with the increased number of resistant strains of bacteria. New agents are needed to combat antibiotic resistance and the management of patients with nosocomial infections, a major cause of morbidity and mortality in hospitalized patients. Two antibiotics were approved in 2001: Cefditoren (Spectracef; Tap pharm) and Ertapenem (Invanz; Merck). Both are broad-spectrum antibiotics and were approved in adults for the treatment of mild to moderate infections (Spectracef) and complicated lower respiratory infections/intra-abdominal infections, etc (Invanz). A novel antibiotic (telithromycin/Ketek) that fights resistant bacteria showed a high level of activity against most organisms affecting the lower respiratory tract, including atypical bacteria received an FDA approvable letter in 2001. Promising in vitro data suggest that Ketek may have a low propensity to induce bacterial resistance. In the drug research and development pipeline, structurally novel inhibitors of bacterial growth include the oxazolidinones (for example, Linezolid - approved 2000), the cationic peptides and the lipopeptide antibiotics (example, Caspofungin - approved in 2001 for the treatment of invasive Aspergillosis).

Finally, sepsis and septic shock continue to be major causes of morbidity and mortality, and no clinical trial has conclusively shown a benefit of suppressing cytokine activation until recently. Drotrecogin alpha (Xigris; Eli Lilly) has shown a reduction in mortality in adult patients with severe sepsis and was approved for clinical use in November 2001.