Rhiza Labs FluTracker Forum

http://abcnews.go.com/Health/wireStory?id=9295024

Health officials in Vietnam are reporting what appears to be the largest cluster yet of Tamiflu-resistant swine flu cases — seven people who traveled together on a long train ride.

Six were from a group of students, and the seventh was in a different train car. They didn't know each other before the train trip in July. They all got sick later, and recovered.

Vietnamese officials reported the cluster in a letter released Wednesday by the New England Journal of Medicine.

Roughly 100 resistant cases have been reported worldwide since the swine flu virus was identified in April. Tamiflu is one of two flu medicines that help. Health officials have been closely watching for signs that the virus is mutating, making the drugs ineffective.

To the Editor: Oseltamivir-resistant infection with the 2009 pandemic influenza A (H1N1) virus has so far been described only rarely and is conferred by the H275Y substitution in the neuraminidase enzyme.1 Only 3 of the 32 patients with oseltamivir-resistant infection reported on as of this writing were not receiving oseltamivir when the resistant viruses were detected, and ongoing community transmission has not yet been shown.1 However, the emergence of oseltamivir-resistant 2009 H1N1 influenza remains a grave concern, since widespread oseltamivir resistance has been observed in seasonal H1N1. This resistance was unrelated to selective drug pressure, and the H275Y substitution did not appear to reduce transmissibility or severity.2,3 We report on a cluster of seven cases of oseltamivir-resistant 2009 H1N1 infection in Vietnam.

In July 2009, during a 42-hour journey, 10 students socialized together in the same train carriage. None of the students knew each other before the journey, none had contact with a person with suspected influenza in the week before the trip, none were symptomatic during the journey, and none were previously or currently receiving oseltamivir. Fever developed in four of the students within 12 hours after arrival and in two more students within 48 hours after arrival (Fig. 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). An additional case was identified in a traveler in a different carriage (Patient G). Nasal swabs, throat swabs, or both from all seven persons were positive for 2009 H1N1 RNA when tested with reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, and viruses were successfully cultured from specimens obtained from three of the persons. The H275Y substitution was detected retrospectively in diagnostic specimens obtained from all seven subjects before any oseltamivir treatment. The concentrations of oseltamivir carboxylate required for a 50% inhibition of neuraminidase activity of the isolated viruses in a fluorometric neuraminidase-inhibition assay were 323.6, 429.5, and 889.2 nM; these concentrations confirmed resistance4 (see the Supplementary Appendix).

Six patients were admitted to a hospital for isolation, one patient was isolated at home, and all were treated with oseltamivir phosphate at a dose of 75 mg twice daily (Fig. 1 in the Supplementary Appendix), since resistance testing had not yet been performed. All patients recovered uneventfully, although one patient (Patient F), with the highest 50% inhibitory concentration, continued to test positive on RT-PCR until day 9, despite receiving oseltamivir from the day of the onset of illness (Fig. 1 in the Supplementary Appendix). An extensive public health investigation did not identify additional patients or the index patient.

In this cluster, infection developed in at least 6 of the 10 people who were probably exposed to the index patient; this shows that resistant 2009 H1N1 viruses are transmissible and can replicate and cause illness in healthy people in the absence of selective drug pressure. Ongoing transmission from the cluster was not detected, but the tracing of all contacts was not possible, so ongoing transmission cannot be ruled out. However, only three other resistant cases have been detected in Vietnam as of this writing, and all were due to selection of resistant viruses during treatment rather than person-to-person transmission. Although data are limited, it is likely that the detected levels of oseltamivir resistance are clinically relevant.5 The loss of oseltamivir as a treatment option for severe 2009 H1N1 infection could have profound consequences. To minimize this risk, the use of oseltamivir should be restricted to prophylaxis and treatment in high-risk persons or the treatment of people with severe or deteriorating illness, antiviral stockpiles should be diversified, and optimal dosages and combination therapies should be urgently studied. Close monitoring and reporting of resistance to neuraminidase inhibitors are essential.

http://content.nejm.org/cgi/content/full/NEJMc0910448

Why does information like this take so long to surface? This occurred in July.

Actually, there was media coverage in August. In fact it was the commentary on H274Y in Vietnam that was linked to my banning at flutrackers.com

http://www.recombinomics.com/News/08250 ... etnam.html

I remember hearing about this for months. Do you sometimes feel like Cassandra, Dr. Niman?

Commentary

http://www.recombinomics.com/News/12100 ... ttack.html

Vietnam has been very much on the ball in proactively trying to protect the Vietnamese people from swine flu.

As to increasing Tamiflu resistance:

"Vietnam to produce Russian-developed swine flu antiviral drug


A research group from the Hanoi University of Pharmacy has said that they would produce an antiviral drug developed by Russia specifically for swine flu and avian flu next year.


Fludon H1, or Arbidol, which has been licensed for manufacture and distribution in many countries, will offer treatment for influenza A (H1N1) virus and H5N1 virus with the same efficiency as Tamiflu and Zanamivir drugs, said Nguyen Hai Nam, who leads the research team.

However, the Vietnamese alternative will be four to five times cheaper than the common Tamiflu, Nam said.

Meawhile, Truong Quoc Cuong, head of the health ministry’s Drug Administration of Vietnam, on Sunday said they had ordered one million 30g doses of Tamiflu for children.

Latest statistics at the Central Hospital of Tropical Diseases showed that children account for three percent of swine flu patients, but antiviral drugs for pediatric patients were not yet available, Cuong said.

Doctors, therefore, have to break the adults’ 75mg dosage of Tamiflu to treat children, he added.

The agency has also placed orders for 10,000 boxes of Relenza (Zanamivir) as an alternative for H1N1-positive patients whose bodies are resistant to or slow to respond to Tamiflu, Cuong said.

He said studies showed patients with this resistance account for six percent of the total, but there was no other drug than Tamiflu available in Vietnam at present.

Since the epidemic was first detected here in May, it has killed 44 people nationwide. A 59-year-old man with mental disorders in the northern province of Quang Ninh was the latest victim, the health ministry said Sunday.

Source: Thanh Nien, Tuoi Tre"

Source: http://www.thanhniennews.com/healthy/?c ... wsid=53999

In contrast to WHO and CDC propaganda head pats trying to say the H274Y is "spontaneous" and "sporatic" and transmission is limited to hospitalized patients.

The emperor has no clothes (or shame).

On the 9th September 2009 the Vietnam National Influenza Center at the National
Institute for Hygiene and Epidemiology (NIHE) sequenced a batch of 85 H1N1
2009 viruses to look for resistance mutations, including S31N in the M2 protein
conferring resistance to the M2 inhibitors (adamantanes) and H275Y in the
neuraminidase that confers resistance to oseltamivir. All 85 viruses contained the
S31N mutation and three contained the H275Y mutation. The three oseltamivir
resistant strains prompted an immediate retrospective public health investigation
that entailed medical note review, tracing and interviews of the three cases and a
review of all pandemic H1N1 case reports for an epidemiological link to the three
cases.
Page 2 of 6
The investigation revealed that the three cases formed part of a cluster of seven
2009 H1N1 cases all linked to a 42-hour train journey between Ho Chi Minh City
and Hanoi in July [Figure 1]. During the trip ten students, who were seated near to
each other but did not know each another prior to the journey, socialized together.
The carriage was not air-conditioned and contained 48 hard seats, most of which
were occupied throughout the journey [Figure 2]. One of the students left the train
after 34 hours, one left after 37 hours (Case D), and the other eight continued to the
final destination of Hanoi. Eight of the ten students could be traced through 2009
H1N1 case records or through email or mobile phone numbers exchanged during
the trip. Six of the traced students had symptomatic H1N1 2009 infection and two
reported no illness. Serology was not done on the two asymptomatic students. The
two untraceable members of the group of students were reported to have appeared
completely well throughout the entire trip. It was not possible to trace the other
occupants of the carriage as passenger names and seat numbers are not recorded.
The seventh case (Case G) was seated in a different carriage to the group of ten
students and had no identifiable contact with them.

This suggests that there were at least TWO transmission events involving H274Y.