High-Tech Battles versus Stubborn Microorganisms

Flu ResearcherTenacious viruses. DNA. Superbugs. All are pieces of today’s influenza and pneumonia puzzle, and all could change the next chapter in the story of very common but potentially lethal diseases.

Influenza and pneumonia combined are the eighth leading cause of death in America, and influenza kills between 300,000 and 500,000 people worldwide annually. Discovering focused diagnostic and treatment tools for both influenza and pneumonia, such as a universal vaccine for influenza and antibiotics that virulent strains of pneumonia will not resist, is a worldwide research challenge.

The H1N1 pandemic snapped into sharp focus the urgency for vaccine development, streamlined public health outreach and vaccine distribution strategies leading to increased immunization rates. Immunization is the answer to influenza prevention, but the current vaccine manufacturing process has many shortcomings and has not greatly changed since its development many decades ago. Under current development techniques, the process is lengthy, and the vaccine must be created annually. How protective the annual flu vaccine is depends upon how closely the serum’s virus strains match those that are actually circulating throughout the population. Effectiveness also can vary based on the age and health status of the individual.

Ultimately, the goal is to create a “universal” flu vaccine—one that has several years’ protection and combats multiple strains, including new viruses that may arise in future. The probability of scientists’ achieving that goal rests in part on their creative use of several novel production technologies to further protect vulnerable populations and to quickly control the spread of potential pandemic influenza viruses. These techniques eventually may revolutionize the development of influenza vaccines.

Cell-based vaccines would replace the current egg-based manufacturing process. Cell-based vaccines would allow scientists to harness wild flu viruses and would ensure that a large quantity of vaccine could be produced quickly in the event of a flu pandemic.  Researchers also are investigating new vaccines based on a multi-functional influenza protein, using an “engineered” flu virus. These vaccines would be given as nasal mist and could be effective against a wider number of viral strains.  DNA-based techniques remain a long-term potential goal for flu vaccine development; they are based on researchers’ cloning the genes that encode specific influenza proteins. These would allow vaccine candidates to be generated as soon as the genetic sequence of strains is known, and the process would eliminate the need to handle pathogenic viruses or to adapt them to grow in eggs or cells.

Antibiotic resistance is a life-threatening challenge often caused by unnecessary overuse.

Pneumonia varies not only by pathogen (viral vs. bacterial), but treatment also may vary according to where a person acquires the pathogen—in the community, hospital or in a long-term healthcare setting. Different bacteria and viruses occur in each setting, and bacteria that occur in long-term healthcare settings are more likely to be resistant to antibiotics. Overarching research efforts are developing new classes of antibiotics and therapies that more effectively treat a range of bacterial pneumonia, including the increasingly virulent, antibiotic-resistant strains.

Antibiotics development overall is stagnant. Very few new classes of antibiotics have been developed in the last several years. Those that have been approved are mostly new versions of existing classes. Development of new classes of antibiotics is costly and does not necessarily financially benefit the manufacturer. The problem of antibiotic resistance, however, is an increasing, life-threatening challenge. Antibiotic resistance is caused mainly by overuse of antibiotics. There are two general reasons for antibiotic overuse: they may be prescribed when not necessary as with the common cold, and they may be prescribed in doses that are more lengthy than may be necessary.   Some of the resistant pneumonias are the result of so-called “superbugs” like methicillin-resistant Staphylococcus aureus (MRSA) and offer a dramatic illustration of the need for research. MRSA, for example, can attack even young individuals and infect them with a very severe form of pneumonia that is extremely difficult to treat with current antibiotics.

The problem of antibiotic resistance permeates treatment strategies for bacterial pneumonia, particularly for healthcare-associated and community-acquired pneumonia. Patients who contract hospital-acquired pneumonia generally are highly susceptible because their immunity is already impaired while they are hospitalized. Prescribing the best antibiotic therapy as quickly as possible for these cases is a challenging treatment goal that could be moved forward with research. People ill with healthcare-associated pneumonia also have particular problems because they, too, are already vulnerable. These include people in nursing homes, who have been re-admitted to a hospital, or undergo center-based dialysis. The research challenge begins with the need for better diagnostic tools for both healthcare-associated and community-acquired pneumonia so that physicians can clearly identify responsible pathogens. With pathogens confirmed, clinicians can prescribe focused therapy and reduce indiscriminate use of antibiotics, which contributes to resistance.

To the general public, influenza and pneumonia may not appear to present major research needs. Medical reality, however, presents the case that investments in these investigations is critical as clinicians grapple with a range of pathogens affecting annual influenza, many varieties of pneumonia and the increasingly urgent issue of treating antibiotic-resistant pneumonias.