Flu Bugs Growing Resistance to Drugs, Studies Find

19 May 2008 (Reuters Health [Maggie Fox])—Seasonal flu viruses are developing the ability to evade influenza drugs globally, but how and why this is happening is not clear, experts told a conference.

Europe is the worst-affected by strains of influenza that resist the effects of antiviral drugs, but the resistance is growing globally, they told a meeting of the Infectious Diseases Society of America.

The resistance also varies by strain, with a quarter of H1N1 flu viruses resistant in Europe and ∼11% of H1N1 in the United States, but far fewer cases of H3N2 and influenza B viruses.

The findings show that flu viruses—already known to mutate speedily—may be even more unpredictable than anyone thought.

Experts fear drugs may become quickly useless to fight an unusually severe flu season or the emergence of a new strain of flu that may cause a pandemic. They have been stressing the need to develop new flu drugs and also quicker and better ways to make vaccines.

The World Health Organization and the US Centers for Disease Control and Prevention (CDC) have been collecting samples of the annual flu viruses to check them against the 4 available flu drugs: amantadine and rimantadine and the newer drugs Tamiflu and Relenza.

The viruses changed rapidly over the past 2007–2008 flu season, Dr. Bruno Lina of Claude Bernard University in Lyons, France said. “We started with something like 10% in Europe.” By April of this year, 25% of the viruses tested were resistant to Tamiflu.

US flu viruses developed a sudden ability to evade the effects of the older drugs amantadine and rimantadine during the 2005–2006 flu season, said Dr. Larisa Gubareva of the CDC. In 2006, the CDC said no one should use those drugs any more.

Doctors had hopes for 2 newer drugs—Roche AG's Tamiflu, known generically as oseltamivir and licensed from Gilead Sciences, and GlaxoSmithKline's Relenza, known generically as zanamivir.

But already resistance is being seen to Tamiflu, a pill that can be taken to treat symptoms and also to prevent infection.

Lina's team tested >2600 samples of flu viruses from patients in Europe and found baffling patterns of this resistance that appeared to have nothing to do with actual use of Tamiflu.

For instance, in France, 54% of those tested in Paris carried the mutation that would give resistance to Tamiflu, compared to 29% in southeastern France. “Which makes absolutely no sense,” Lina said.

Patients showed no difference in their symptoms if they were infected with resistant virus, he noted.

And in Europe, the H1N1 viruses were the most resistant.

Gubareva said tests across the United States, Canada, and Mexico showed very quick development of drug resistance among H1N1 viruses. As of May 15, resistant viruses had been detected in 18 US states out of 43 where virus samples from patients were tested, she said.

In Canada, resistant virus was found in 9 of 13 provinces.

But only 6% of H3N2 and influenza B samples tested in North America had genetic mutations giving resistance to Tamiflu, she said. (Editing by Michael Kahn and Jackie Frank)

Multistate Outbreak of Human Salmonella Traced to Tainted Dog Food

15 May 2008 (Reuters Health)–Contaminated dry dog food was the source of an outbreak of Salmonella infections affecting individuals in 19 states, public health officials report in the Morbidity and Mortality Weekly Report for 16 May.

The first 3 cases of infection reported in Pennsylvania in May 2006 involved identical strains of Salmonella enterica serotype Schwarzengrund. By October 2007, a total of 70 laboratory-confirmed human cases of the outbreak strain of S. Schwarzengrund had been reported to the Centers for Disease Control and Prevention (CDC).

According to Dr. A. Ferraro, at the Pennsylvania Department of Health, and colleagues, the largest numbers of reported cases were in Pennsylvania (29 cases), New York (9 cases), and Ohio (7 cases). Median age of infected patients was 3 years (range, 1 month–85 years); 39% of cases were <1 year of age.

A multistate case-control study, as well as cultured specimens of dog stool and bags of dry dog food, implicated a manufacturing plant in Pennsylvania, which produces ∼25 different brands of dry pet food.

An inspection of the plant turned up 1 isolate of the outbreak strain on an environmental surface and 2 isolates in 2 brands of dry dog food. The manufacturer recalled these 2 brands, but only in the sized bags from which the bacteria were isolated, and suspended operations between July and November for cleaning and disinfection.

In an editorial note, the CDC points out that only ∼3% of Salmonella infections are laboratory confirmed and reported to pubic health authorities, so the outbreak was probably much larger than the 70 reported cases would indicate.

Moreover, the limited recall by the manufacturer means that contaminated dry pet food is almost certainly still present in many homes.

To prevent Salmonella infections, the CDC makes the following recommendations:

• “Persons should wash their hands for at least 20 s with warmwater and soap immediately after handling dry pet foods, pet treats, and pet supplements, and before preparing food and eating.”

• “Infants should be kept away from pet feeding areas.”

• “Children aged <5 years should not be allowed to touch or eat pet food, treats, or supplements.”

Source: Morb Mortal Wkly Rep CDC Surveill Summ 2008; 57:521–4.

Novartis MenB Meningitis Vaccine Protects Infants

14 May 2008 (Reuters Health)—Novartis AG's MenB vaccine showed potential to give broad protection to infants against meningococcal B infections in a mid-stage study, the Swiss drugmaker said.

Results from the phase II trial, presented at the European Society for Paediatric Infectious Diseases meeting in Austria, showed a series of 3 immunizations with MenB starting at 2 months of age produced a protective immune response.

The meningococcal B strain causes 72% of meningitis infections in Europe.

Editor's comment. The capsular polysaccharide of the B serotype of meningococcus is poorly antigenic and is not included in any of the vaccines available in the United States. Although type B meningitis is a major problem in Europe and some other areas of the world, it is responsible for only a minority of cases of meningococcal meningitis in the United States. However, it would clearly be advantageous to have B antigen included in the US vaccines, if it could be made sufficiently antigenic to provoke a good antibody response.

The significance of the vaccine described above is that, unlike the polysaccharide vaccines available in the United States, it uses outer membrane antigens and is apparently antigenic even in infants. The US polysaccharide vaccines are not effective in children <2 years of age. Although not availably commercially, an outer membrane B vaccine was supplied by the government and was widely used in New Zealand because of a type B epidemic. (D.K.)

British Company Developing Nasal Gel MRSA Drug

19 May 2008 (Reuters Health)—British researchers are working on a new drug, which is placed as a gel in the nose, that may offer new hope in the fight against the hospital superbug methicillin-resistant Staphylococcus aureus (MRSA).

Destiny Pharma, a privately owned biotechnology company in Brighton, said on [18 May] its experimental drug XF-73 had destroyed virulent strains of MRSA in laboratory studies, without any signs of resistance developing.

“Results suggest that XF-73's remote resistance profile may allow widespread MRSA decolonization in hospitals to support national initiatives for effective infection control,” it said in a statement.

Tests found that MRSA did not develop resistance to the medicine, despite being exposed to it 55 times.

The drug works in a different way to conventional antibiotics. It interacts lethally with the bacteria's cell membrane, giving bugs less opportunity to develop pathways to escape its effect.

Destiny, which has completed initial phase I clinical trials, presented its findings to the European Congress on Clinical Microbiology and Infectious Diseases in Barcelona last month.