WHO Probes China's Reported Use of Flu Drug on Birds

20 June (Reuters Health)—The World Health Organization (WHO) is seeking clarification from China about reports it urged farmers to use a human antiviral drug to treat birds infected with a deadly strain of avian flu, breaking international guidelines.

The Washington Post reported that Chinese farmers, acting with government encouragement, had tried to suppress major bird flu outbreaks among chickens with amantadine, possibly making it useless in fighting human influenza.

Researchers had determined that the H5N1 bird flu strain in Vietnam and Thailand had become resistant to amantadine, the Post said, adding they suspected it had been due to the drug's use on farms.

The Post, quoting international researchers, said the drug would no longer protect people in case of a worldwide avian flu epidemic.

The WHO has said the virus that first surfaced in poultry in Hong Kong and China 8 years ago is “unstable, unpredictable, and very versatile.”

It has killed at least 37 people in Vietnam, 12 in Thailand, and 4 in Cambodia. China has culled thousands of birds this year to curb the spread of the disease.

Editor's comment. At last we have a possible explanation for amantadine resistance in the H5N1 strain of influenza virus. It is a good thing that the high cost of oseltamivir prevented its use as bird feed.

China's Ministry of Agriculture has officially stated that the government had never approved the use of amantadine in birds and that it was well aware of the risks associated with such use. However, reading between the lines of the statement reveals that it is likely that some farmers may have used amantadine.

However, the scope of amantadine use would probably be limited in China because of its high cost. Poultry vaccines against H5N1 are available in China, are administered once every 6 months, and are inexpensive. These vaccines are distributed free of charge to some institutions (such as veterinary departments), and if some farmers buy the vaccines on their own, they can receive subsidies or compensation.

Cheese from Mexico Linked to M. bovis Infections in New York

24 June (Reuters Health)—Fresh cheese made from unpasteurized cow's milk from Mexico appears to be the source of several cases of Mycobacterium bovis infection in New York City, Centers for Disease Control and Prevention investigators report.

Following the death of a 15-month-old boy in March 2004 due to peritoneal infection by M. bovis, Dr. A. Winters, from the New York City Department of Health and Mental Hygiene, and colleagues investigated 35 cases of human M. bovis infection identified in that city since 2001. They report their findings in the Morbidity and Mortality Weekly Report.

The results of a rapid genotyping test— spoligotyping—revealed that M. bovis comprised 1% of 3417 cases of cultureconfirmed tuberculosis between 2001 and 2004, including 12 cases in children <15 years old and 5 in children <5 years old. Further testing showed that a cluster of 13 isolates were identical.

All but 1 of the 35 isolates were resistant to pyrazinamide. Fourteen were also resistant to streptomycin, 1 was resistant to isoniazid, and 2 were resistant to isoniazid and streptomycin.

Eleven patients were born in the US, while the rest were born in Mexico, the Dominican Republic, Guatemala, or Guyana. All of the patients <5 years old were born in the US of parents from Mexico.

The investigators interviewed 23 patients or their parents and found no linkages suggestive of airborne, person-to-person transmission of M. bovis. However, 19 reported having eaten cheese produced in Mexico while they were living the US.

The authors note that in a previous study, 17% of cattle tested in Mexico were infected with M. bovis, and that 20% of cow's milk in Mexico used for fresh cheese is not pasteurized.

Source: MMWR Morb Mortal Wkly Rep 2005; 54:605–8.

New Version of Nasal Flu Vaccine Shows Promise

16 June (Reuters Health)—MedImmune Inc. said that an easier-to-store version of its nasal spray flu vaccine FluMist met the main goal of a late-stage trial, which was to show that it worked as well as the approved version in protecting against the flu.

FluMist, which was approved in 2003, has had disappointing sales, in part because it needs to be kept frozen. The new version, called CAIV-T, only needs to be kept refrigerated. The company hopes to file for regulatory approval for CAIV-T in healthy people ages 5 to 49.

MedImmune said the phase III study included 980 people who received either CAIV-T or FluMist. The results showed equivalent antibody levels after vaccination. FluMist is not approved for very young children or the elderly. The company is working on additional studies to assess CAIV-T in children 6 months to 5 years of age.

Cubicin Meets Primary End Points in Staphylococcus aureus Endocarditis/ Bacteremia Study

27 June (Business Wire)—Cubist Pharmaceuticals, Inc. announced that its phase 3 Staphylococcus aureus (S. aureus) endocarditis and bacteremia trial of daptomycin at 6 mg/kg once daily met its primary end points of noninferiority in the intent-to-treat (ITT) and per protocol (PP) populations. Cubist expects to file a supplemental New Drug Application (sNDA) before year-end seeking priority review for approval to add S. aureus endocarditis and bacteremia to the indication statement for Cubicin.

Dr. Ralph Corey, Chair of the Independent External Adjudication Committee, Professor of Medicine and Infectious Disease at Duke University Medical Center and Director of Infectious Disease at Duke Clinical Research Institute said, “This was an exceptionally complicated study to design and execute.With the data it has generated, it sets the standard for registration quality studies of S. aureus endocarditis and bacteremia.”

This is the first-ever successfully executed registration study of endocarditis and bacteremia expressly focused on S. aureus. There were 235 patients in the ITT population and 139 patients in the PP population (patients who completed the specified treatments and evaluations according to protocol). In the ITT population 23% of patients were diagnosed with S. aureus endocarditis and 51% were diagnosed with complicated S. aureus bacteremia, with balanced representation between the 2 treatment arms. Thirty-seven percent of the Cubicin-treated patients in this population were infected with methicillin- resistant S. aureus (MRSA), and 38% of the patients in the comparator arm were infected with MRSA.

The overall Cubicin success rates in the ITT and PP populations were higher than the success rates seen in the comparator arm with the greatest difference in success rate observed in the subset of patients with MRSA, although the differences were not statistically significant.

In the trial the most common adverse events, among ⩾15% of patients, in both the Cubicin (6 mg/kg per day dose) and comparator arms included musculoskeletal symptoms, nausea and vomiting, and edema. Other adverse events seen in ⩾15% of comparator-treated patients included diarrhea, potassium imbalance, anemia, and renal failure or impairment.

Editor's comment. We look forward to the peer-reviewed publication of this study. The question of greatest importance is whether daptomycin is superior to vancomycin. The most important subset is the MRSA-infected patients with endocarditis who were in the PP group. I would assume that the comparator group was mainly treated with vancomycin. On the basis of the numbers given, there would seem to be a minority of patients with MRSA infection and a minority of patients with endocarditis.With only 139 patients in the PP group, it may be difficult to draw any convincing conclusions.

Polio Spreads to Angola, Indonesia's Sumatra—WHO

1 July (Reuters Health)—Angola has reported its first case of polio in 4 years, and the crippling disease has also spread within Indonesia to Sumatra island, the World Health Organization (WHO) said on Friday.

The paralysis of a baby girl in the Angolan capital Luanda and of a 3-year-old girl in Lampung province on Sumatra, Indonesia's 66th case since an outbreak began in May, are fresh blows to its bid to halt the global spread of polio by yearend.

Polio reemerged in May in Indonesia, which had been polio-free since 1995. The first case was near the West Java city of Sukabumi, 100 km (60 miles) south of Jakarta, but the latest case means the virus has jumped westward from the main island Java to Sumatra.

Angola is the 17th previously polio-free country to be reinfected since 2003, when the virus began circulating widely in Africa, according to the United Nations health agency.

But genetic analysis has shown it was imported from India, also an endemic region, not from Nigeria, where a 10-month ban on vaccination in the northern state of Kano is blamed for the virus spreading across Africa, reaching Saudi Arabia and Yemen.