Date: Sat 8 Aug 2009
From: Rogier van Doorn <rvandoorn@oucru.org> [edited]
In the Hospital for Tropical Diseases [HTD] in Ho Chi Minh City, Viet
Nam, patients with flu symptoms and a positive real time polymerase
chain reaction (RT-PCR) result for influenza pandemic H1N1 2009 virus
infection using the CDC assay (inc. specific A(H1N1)v primers/probe)
are hospitalized and treated with oseltamivir (75 mg twice daily)
until RT-PCR results are negative.
We previously reported clinical data and results of daily RT-PCR
testing on the 1st 44 patients identified during the influenza
pandemic (H1N1) 2009 virus outbreak [see ProMED-mail Influenza
pandemic (H1N1) 2009 - Viet Nam: patient data, archive number
20090708.2450]. These results indicated that the majority of patients
had resolved infection by day 2 post admission. 8 patients still had
a positive PCR at day 3, 8 patients had a positive PCR at day 4, and
all were RT-PCR negative by day 5 of sampling.
Subsequently, we have conducted culture attempts on all samples from
the 13 patients that remained RT-PCR positive until day 3 or 4 using
MDCKSiat1 cells in a 6-well plate format, with 3 passage attempts per
specimen. Replicating virus was recovered from 91 percent (10/11) of
day 0 samples; 55 percent (6/11) of day 1 samples; 31 percent (4/13)
of day 2 samples; 46 percent (6/13) of day 3 samples; and [29]
percent (2/7) of positive day 4 samples.
In addition, we have observed a small number of patients that
remained RT-PCR positive for an extended period of time, despite
receiving a full course of oseltamivir treatment (5d of 75 mg twice
daily). Notably, among a total of 297 H1N1 cases diagnosed at HTD to
date (as of 6 Aug 2009), 2 patients remained RT-PCR positive until
day 6, one until day 10, one until day 11, and one until day 12 after
diagnosis/admission to our hospital. However, culture attempts were
negative from all patient specimens collected more than 5 days
post-admission. A neuraminidase inhibition assay was performed on 23
specimens from 16 patients who had a positive PCR at day 3 or later,
and all were found to be fully sensitive to oseltamivir. In addition,
sequencing of selected 1st and last positive specimens from these
patients has failed to reveal presence of the oseltamivir resistance
marker NAH274Y.
Our results show that among these 1st 44 influenza pandemic (H1N1)
2009 virus infected patients diagnosed in Ho Chi Minh City, favorable
clinical and RT-PCR responses were observed. For most patients with
prolonged RT-PCR positive results, replicating virus disappeared
before RT-PCR became negative. Most importantly, among a total of 297
patients no virus was cultured after 5 days of treatment and no
resistance associated mutations were detected.
--
Juliet Bryant
Tran Tinh Hien
Nguyen Thanh Truong
Nguyen Van Vinh Chau
Jeremy Farrar
Rogier van Doorn
Hospital for Tropical Diseases
South East Asia Infectious Disease Clinical Research Network
Oxford University and Wellcome Trust Major Overseas Programme
190 Ben Ham Tu, District 5
Ho Chi Minh City
Viet Nam
<rvandoorn@oucru.org>
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