Vietnam detects 3 cases of drug-resistant swine flu

[Gert van der Hoek]

Vietnam detects 3 cases of drug-resistant swine flu

Mon Oct 12, 2009

HONG KONG, Oct 12 (Reuters) - Vietnam has detected three cases of swine flu that were resistant to the antiviral drug Tamiflu, but an expert said there was no evidence the mutant strains had infected other people.

The three were admitted to the Hospital for Tropical Diseases in Ho Chi Minh city in late August and September and have all recovered, said Rogier van Doorn, a clinical microbiologist and doctor at the hospital.

"The viruses that were isolated when they were admitted were still sensitive (to the drug), but during treatment with oseltamivir, resistance built up," said van Doorn, referring to the generic form of Tamiflu.

"So it was not transmission of resistant viruses, but we observed that it developed during treatment of these three patients ... we have no evidence to show that (there was further transmission of resistant viruses)," he told Reuters.

Tamiflu is made by Roche (ROG.VX) and Gilead Sciences Inc (GILD.O) and is one of two drugs shown to work well against H1N1 swine flu.

The three drug-resistant cases were among more than 600 H1N1 patients who were treated at the hospital.

Two of the patients had very mild disease and the third, a 3-year-old child, was admitted to intensive care but made a full recovery within 10 days.

Tamiflu-resistant swine flu cases have been reported in Japan, Hong Kong, Denmark and the United States.

Flu viruses are mutation-prone and experts are not surprised that they would evolve resistance, just as bacteria develop resistance to antibiotics.

However, experts fear such resistance may spread and complicate efforts to treat victims with the approach of what is likely to be a second wave of swine flu infections as the Northern Hemisphere enters the winter season.

http://www.reuters.com/article/rbssHealthcareNews/idUST22356420091012

[Giuseppe]

Re: Vietnam detects 3 cases of drug-resistant swine flu

INFLUENZA PANDEMIC (H1N1) 2009 - VIET NAM, VIRUS CLEARANCE (from ProMedMail.org, edited)


INFLUENZA PANDEMIC (H1N1) 2009 (68): VIET NAM, VIRUS CLEARANCE

A ProMED-mail post <http://www.promedmail.org>

ProMED-mail is a program of the International Society for Infectious Diseases <http://www.isid.org>

Date: Sun 11 Oct 2009
From: Rogier van Doorn <hrogier@gmail.com>


The following are our follow-up data on 292 patients treated for influenza pandemic (H1N1) 2009 virus infection in South Viet Nam.

In previous ProMED-mail posts (see: Influenza pandemic (H1N1) 2009 (27): Viet Nam, patient data update 20090809.2819, and Influenza pandemic (H1N1) 2009: Viet Nam, patient data 20090708.2450),
we reported clinical, RT-PCR and viral culture data from 44 patients.

Viet Nam had a policy of screening at airports and quarantining of patients that were found positive for pandemic (H1N1) 2009 virus infection until PCR negative, providing an opportunity to study viral dynamics in a population of patients
that would normally not be hospitalized or followed-up on as frequently as was done now.

We believe these data are important and should be shared with the infectious diseases community as soon as possible, as systematic viral clearance data are lacking from the present literature but are of importance both for
healthcare workers and quarantine/containment policy makers.

In addition, we present the 1st 3 cases of selection of H274Y oseltamivir-resistant virus during treatment in Viet Nam.

We previously (20090708.2450 and 20090809.2819) reported on 44 patients with pandemic influenza virus A(H1N1)v infection. We report now what we believe to be the 1st systematic viral clearance data in a large group of
patients with A(H1N1)v infection.

Our hospital was the primary site for quarantine and treatment of patients in southern Viet Nam, either admitted through temperature checks at the airport and subsequent RT-PCR or through outpatient clinics.

Patients were quarantined, treated with oseltamivir 75 mg twice per day for at least 5 days and were sampled frequently (initially daily, later after 0-3-5 days of treatment) by nose/throat swabs.
Patients were discharged when the RT-PCR was negative.

We now present data for the 1st 292 consecutive patients hospitalized between 29 May and 28 Jul 2009. The average age of the patients was 26.4 years (1-69), 110 female and 182 male (includes a large outbreak [n=50] in a
secondary school for boys). 116 patients were Vietnamese residents, and 176 were travellers arriving from foreign countries (67 Australia, 43 USA, 15 Singapore, 14 Thailand, 5 Canada, 5 Germany, 37 other).

Fever was present in 96 percent (281/292), cough in 59 percent (171/292), runny nose in 17 percent (49/292), sore throat in 23 percent (68/292), and diarrhoea in 2 percent (5/292). 27 rectal swabs taken from
patients with and without diarrhoea were all PCR negative

After 24 hours of admission, 78 percent (228/292) of patients had a normal temperature. All patients had a mild illness course. Only one patient had infiltrative lesions on chest X-ray.


Viral PCR was positive for all patients on admission. RT-PCR was positive for the following percentage (n/total n) of patients:
</pre>

• Day of Treatment (DOT) 1: 86 percent (165/192),
  
• DOT2: 59 percent (45/76),
• DOT3: 38 percent (27/72),
• DOT4: 25 percent (34/138),
• DOT5: 14 percent (11/76).

After 5 days of treatment, 7 percent (12/179) still had a positive RT-PCR. One patient remained RT-PCR positive on day 8 and one patient on day 14. We could not isolate a virus after days 5 of treatment in any patient, including
those who were RT-PCR positive (n=12).

In this series of 292 patients, the H274Y neuraminidase mutation, associated with oseltamivir resistance was not detected. We have, however, detected the H274Y mutation in 3 samples from more recent patients.
These 3 patients shed virus for 5, 6 and 11 days after onset of treatment initiation. The mutation was acquired [selected?] during treatment. The clinical course of illness in 2 patients was unremarkable.
One patient, a 3-year-old child, required admission to Intensive Care but made a full recovery within 10 days.

Our results suggest that most patients infected with the pandemic (H1N1) 2009 virus become RT-PCR negative within 5 days of starting 75 mg twice per day of oseltamivir. RT-PCR can remain positive for longer,
but viral culture was negative in all samples from patients still RT-PCR positive after 5 days of treatment. We found the H274Y mutation present in samples from 3 patients (around 50 patients, RT-PCR positive
after 5 days of treatment, [who] were screened from over 600 patients).

We believe this to be the largest systematic assessment of viral clearance dynamics and presence of the H274Y mutation in A(H1N1)v infected patients.

Authors: Tran Tinh Hien, Juliet E Bryant, Nguyen Thanh Truong, Nguyen van Vinh Chau, Tran Thuy Ngan, Vo Minh Hien, Tran Tan Thanh, Jeremy Farrar and Rogier van Doorn

Hospital for Tropical Diseases, Ho Chi Minh City South East Asia Infectious Diseases Clinical Research Network

--
Rogier van Doorn
Hospital for Tropical Diseases
Wellcome Trust Major Overseas Programme
Oxford University Clinical Research Unit
190 Ben Ham Tu
District 5
Ho Chi Minh City
Viet Nam
<hrogier@gmail.com>

[ProMED-mail thanks Rogier van Doorn and colleagues for providing this update on their research on the dynamics of clearance of pandemic (H1N1) 2009 virus infection. - Mod.CP]

[see also:
Influenza pandemic (H1N1) 2009 (27): Viet Nam, patient data update
20090809.2819
Influenza pandemic (H1N1) 2009: Viet Nam, patient data 20090708.2450]
.............................................cp/msp/dk

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