U.S. F.D.A., Roche Warn on Tamiflu Dangers

4 March 2008 (Reuters Health)—US regulators and Roche Holding AG have warned doctors of psychiatric events, some of which resulted in death, in patients taking the flu drug Tamiflu (oseltamivir), regulators said.

Drugmaker Roche wrote a letter, dated February 2008, to health professionals advising them of a recent update to the Tamiflu label, according to a notice posted on the Food and Drug Administration's (FDA's) Web site.

The revised label includes a new description of reports of delirium and other abnormal behavior, with some cases resulting in fatal outcomes, the letter said. The previous language did not mention any deaths.

The new label says the cases “appear to be uncommon” and “the contribution of Tamiflu to these events has not been established.”

The company said the revisions reflect recommendations made in November 2007 by an FDA advisory panel that reviewed the cases, which have been seen mostly in Japan.

“The changes to the label reflect observations from a growing body of data, which shows no evidence of a causal relationship between Tamiflu and the reported adverse events,” Roche said in a statement.

The new label also notes influenza itself can be associated with various psychiatric problems.

Editor's comment. A warning has also been added to the labeling of Relenza (zanamivir) about reports of delirium and abnormal behavior in some patients who took the drug for influenza. (D.K.)

Global Supply of Yellow Fever Vaccine Depleted—W.H.O.

27 February 2008 (Reuters Health)—Yellow fever kills tens of thousands each year, and the world's supply of vaccine is under extreme pressure, a senior World Health Organization (WHO) official said.

The WHO relies upon 3 prequalified manufacturers of yellow fever vaccine: France's Sanofi-Aventis, Senegal's Institut Pasteur, and Bio-Manguinhos in Brazil.

The current global production capacity is 30–35 million doses, Ryan said.

The WHO has dispatched vaccines to Paraguay and Brazil in recent months to contain outbreaks of the mosquito-borne disease in those Latin American countries, drawing on the stockpile from which mass vaccination campaigns for African nations, such as Senegal, Togo, Cameroon, and Burkina Faso, are drawn.

Ryan said it was important for the vaccines, which cost 60 US cents each, to be replenished quickly and maintained at healthy levels.

“We do need to ensure better security in the number of manufacturers we have and the scale of production available,” he told the teleconference.

Yellow fever is named after the jaundice that affects some of those infected with the viral haemorrhagic disease. The WHO estimates that 200,000 people catch yellow fever each year, and 30,000 die as a result.

Editor's comment. For those who have not been following it, there has been a major outbreak of yellow fever in both Brazil and Paraguay in recent months. (D.K.)

All U.S. Kids Should Get Flu Vaccine, Panel Says

27 February 2008 (Reuters Health)—All US children aged from 6 months up to 18 should be immunized every year against influenza, a panel of federal vaccine advisers said.

The vote from the Advisory Committee on Immunization Practices would expand recommendations from the current advice that US children aged 6 months to 5 years old be vaccinated.

The panel, which advises the US Centers for Disease Control and Prevention on vaccine matters, voted at a regular meeting in Atlanta and said the new recommendations should go into effect as soon as possible, but no later than the 2009–2010 flu season.

This year's flu vaccine is considered a poor match for 2 of the strains. Because the virus mutates so quickly, the vaccine is usually formulated afresh each year and includes 3 different strains of the virus.

Editor's comment. I am curious as to why we don't bite the bullet and also recommend influenza vaccination for all persons aged >18 years. In my opinion, vaccination could significantly reduce the influenza burden for those not now immunized and, perhaps more importantly, could reduce the exposure for immunosupressed or elderly persons who do not respond adequately to the vaccine. (D.K.)

G.S.K. Bird Flu Vaccine Shows Broad Cross Protection

3 March 2008 (Reuters Health [Tan Ee Lyn])—A vaccine designed by GlaxoSmithKline (GSK) to protect people against the H5N1 bird flu may be effective in warding off a few different subtypes of the virus, the company said.

In an Asian clinical trial involving 1206 adults in Hong Kong, Singapore, Taiwan, and Thailand, the vaccine produced antibodies that not only neutralized the H5N1 virus found in Vietnam, but also the variant now dogging Indonesia.

“The vaccine was made using the Vietnam strain. In principle, there is a very broad antibody reactivity that's being induced. These are neutralizing antibodies, and they do correlate with protection,” Albert Osterhaus, head of virology at the Erasmus Medical Centre in The Netherlands, told Reuters when asked for comments about the study.

Osterhaus was not involved in the study but is familiar with the results and methodology.

An earlier GSK study in Europe showed the vaccine to be effective in protecting against 2 other H5N1 subtypes, in China's central eastern province of Anhui and Turkey.

An eventual vaccine to protect people against a flu pandemic can only be made 4–6 months after the start of such a disaster, when the culprit virus strain has been identified.

But human populations still need some form of protection in those initial months of a pandemic, and drug companies are in a race to design what are known as “prepandemic” vaccines.

GSK's prepandemic vaccine uses a very low dose, 3.8 µg, of antigen.

Volunteers in the GSK trial received 2 shots of the adjuvanted vaccine 21 days apart, and blood tests done 3 weeks after the second shot showed the presence of antibodies which neutralized the Vietnam and Indonesian H5N1 strains.

Osterhaus, however, voiced a note of caution—that the pandemic may be triggered by a completely different virus.

(Edited by Jerry Norton)

Multidrug-Resistant Tuberculosis Reaches New High

26 February 2008 (Reuters Health)—A report by the World Health Organization (WHO) indicates that rates of multidrug-resistant tuberculosis (MDR-TB) are now at their highest level ever. Each year there are nearly half a million new cases of MDR-TB, the WHO estimates, which is roughly 5% of the total 9 million TB cases seen annually.

The report, “Anti-Tuberculosis Drug Resistance in the World,” is based on the largest survey to date on the occurrence of drug-resistant TB globally. Data from 90,000 TB patients in 81 countries were collected between 2002 and 2006.

The survey also marks the first time that rates of extensively drug-resistant TB (XDR-TB), a nearly untreatable form of the disease, were determined. The findings are not encouraging: XDR-TB was identified in more than one-half of the countries studied.

“TB drug resistance needs a frontal assault. If countries and the international community fail to address it aggressively now, we will lose this battle,” Dr. Mario Raviglione, Director of the WHO Stop TB Department, said in a statement.

“In addition to specifically confronting drug-resistant TB and saving lives,” he added, “programs worldwide must immediately improve their performance in diagnosing all TB cases rapidly and treat them until cured, which is the best way to prevent the development of drug resistance.”

Baku, the capital of Azerbaijan, had the highest rate of MDR-TB: nearly one-quarter (22.3%) of all TB cases were resistant to multiple agents. High rates were also recorded in Moldova (19.4%), Donetsk in Ukraine (16%), Tomsk Oblast in the Russian Federation (15%), and Tashkent in Uzbekistan (14.8%). All of these rates are higher than the highest rate recorded in the last WHO TB report released in 2004.

Surveys also suggest that MDR-TB is widespread in China, the WHO notes.

The true global burden of MDR-TB, however, is unknown because many countries do not have surveillance systems in place or are unable to test for drug resistance. For instance, Africa has the highest rates of TB in the world, yet only 6 countries could contribute drug resistance data to the current report.

Consistent with prior studies, the survey indicates a link between HIV infection and MDR-TB. Data from Latvia and Donetsk, Ukraine, indicate that HIV infection nearly doubles the risk of MDR-TB.

Not all of the news was bad, however. Estonia and Lavia, 2 countries considered drug-resistant TB “hotspots” 13 years ago, have made significant strides. With a substantial investment and focused assault on MDR-TB, rates in these countries have now stabilized, and TB case notification rates are declining.

According to the WHO, ∼$4.8 billion will be needed to achieve overall TB control in low- and middle-income countries this year. This includes $1 billion needed to control MDR-TB and XDR-TB. The WHO estimates that current contributions fall short of the amount by $2.5 billion.