Hong Kong: Two Hospital Clusters Of MDR Acinetobacter Infections

Credit CDC PHIL

 

# 8856

 

Because it is such an international city, and boasts one of the most diligent (and open) public health agencies in the world (Centre For Health Protection), Hong Kong has become a terrific  barometer for the growth of multiple drug resistant infections from around the world.

 

One of the toughest bacteria that hospitals must deal with is called multidrug-resistant (MDR) Acinetobacter baumannii, which in recent years has made headlines as the cause of difficult to treat wound infections among our troops serving in the Middle East.

 

Acinetobacter (of which there are many varieties, but A. baumannii is most often linked to human infection ) are ubiquitous in nature, and can be found in soil, water, animals and humans. A very hardy species, they can survive for extended period of time on inanimate surfaces, making them difficult to control in a health care setting (see AJIC report Hospital cleaning protocol ineffective against A. baumannii)..

And like with MRSA, many people can be colonized, but not show signs of infection.  Often very serious infections develop among those who are very ill, wounded, or immunocompromised.

 

Today Hong Kong’s CHP has published two reports on hospital clusters of MDR  Acinetobacter infection.

 

Cluster of Multi-drug Resistant Acinetobacter cases in Queen Elizabeth Hospital

The following is issued on behalf of the Hospital Authority:

The spokesperson for Queen Elizabeth Hospital (QEH) made the following announcement today (July 22):

Five male patients (aged 35 to 80) of a Ventilator Ward have been confirmed as having Multi-drug Resistant Acinetobacter (MDRA) since July 14. Two of them are infected cases and are still hospitalised at QEH. The remaining three patients were confirmed to be MDRA carriers without clinical symptoms. Out of these cases, two are still hospitalised under medical surveillance and isolation at QEH. The remaining patient has been transferred to Hong Kong Buddhist Hospital. All of the five patients are in stable condition.

(Continue. . . )

Cluster of Multi-drug Resistant Acinetobacter cases in Caritas Medical Centre

The following is issued on behalf of the Hospital Authority:

     The spokesperson of Caritas Medical Centre made the following announcement today (July 22):

Three patients (aged 37 to 88) of a male Medicine and Geriatrics Ward have been confirmed as having Multi-drug Resistant Acinetobacter (MDRA) since July 17. Two of them are infected cases. The patients are still hospitalised under medical surveillance and isolation. Two of them are in stable condition, while the other one is in serious condition.

(Continue . . .)

 

 

Just yesterday, Hong Kong reported a Case of NDM-5 Carbapenemase-producing Enterobacteriaceae under CHP investigation in a 30-year-old woman with a urinary tract infection.  

 

NDM-5 is a novel variant of the NDM-1 enzyme which first made headlines four years ago when  The Lancet published a study (see NDM-1: A New Acronym To Memorize)  by Walsh, Toleman, Livermore, et al.  on the emergence and growing prevalence of the antibiotic resistant enzyme on the Indian sub-continent.

While still relatively rare – at least in the United States and Europe – this growing rogues gallery of new, multi-drug resistant organisms continues to gain traction around the world, threatening an early demise for much of our current antibiotic arsenal. 

 

In early 2012 World Health Director-General Margaret Chan expressed a dire warning about our dwindling antibiotic arsenal (see Chan: World Faces A `Post-Antibiotic Era’) – a sentiment echoed a year later by CDC Director Thomas Frieden during the release of a major US report on the threat (see McKenna On CDC Antibiotic Resistance Report).

 

Dark, if not Inevitable conclusions, backed up by a long list of reports and studies showing the inexorable erosion the effectiveness of our current antibiotics to deal with rapidly evolving bacteria.   Some of these reports I’ve covered in the past include:

 

EID Journal: Acquisition of Drug Resistant Genes Through International Travel

AAP/CDC: New Guidance On For Antibiotics For Children

The Lancet: Antibiotic Resistance - The Need For Global Solutions

UK CMO: Antimicrobial Resistance Poses `Catastrophic Threat’

MMWR Vital Signs: Carbapenem-Resistant Enterobacteriaceae (CRE)

 

 

For a more complete look at the complex issues of antibiotic resistance, and the dearth of new drugs on the horizon, I can think of no resource better than Maryn McKenna’s superb book (and recent winner of the 2013 June Roth Memorial Book Award, American Society of Journalists and Authors) Superbug: The Fatal Menace of MRSA.

And while I dabble in writing about the issues of antibiotic resistance, undoubtedly the best coverage can be found on Maryn’s Superbug blog.

The MERS Hospital Cluster Puzzle

R0 (pronounced R-nought) or Basic Reproductive Number.

Essentially, the number of new cases in a susceptible population likely to arise from a single infection. With an R0 below 1.0, a virus (as an outbreak) begins to sputter and dies out. Above 1.0, and an outbreak can have `legs’.

 

# 8490

 

Two months ago, in mBio: Spread, Circulation, and Evolution of MERS-CoV, we looked at a study that focused on the evolutionary changes in the MERS coronavirus since its introduction to the human population, and its apparent efficiency in transmitting between humans.

 

At the time, based on 180 human cases reported over roughly 18 months, the authors determined that the MERS virus had an R₀ of less than 1.

In other words, it wasn’t spreading efficiently enough to sustain an ongoing epidemic.

They warned, however, that over time evolutionary pressures could allow the virus to better adapt to human hosts, writing:

 

MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus.

 

Fast forward 60 days, and suddenly we are seeing at least two large clusters of MERS – one in the UAE (12 cases) and the other in Jeddah, Saudi Arabia (45 cases) – and of particular note, both involve a large number of healthcare workers. 

 

A cohort that, at least in theory, should be practicing stringent infection control protocols. 

 

While we don’t have the specifics on the source of the initial infection or the subsequent chain of transmission in either cluster, their size and duration are at least suggestive of more robust transmission. 

 

Dr. Ian Mackay’s chart from earlier this week (see below) illustrates this sudden jump in cases counts in KSA and the UAE. 

 

All of which begs the $64 question: Has something changed with the virus?

 

It is a question raised by Dr. Michael Osterholm – Director of CIDRAP - yesterday (see Osterholm & Mackay On MERS), and one that has been on the minds of many watching the evolution of these two large clusters.

 

Definitive answers to that question may be some time in coming, as it will require detailed genetic analysis and an in-depth epidemiological investigation to establish the facts. It isn’t, however, the only possible explanation.

Another possibility is that we are seeing a couple of `super spreader’ events, reminiscent of what was seen in Al-Hasa a year ago (more on that later). 

 

During the SARS epidemic of 2003, we know that transmission of that coronavirus was typically fairly inefficient.

 

An infected person might only infect 1 or 2 additional people, and sometimes none.  But a small percentage of those infected were far more efficient in spreading the disease, with some responsible for 10 or more secondary infections.

This super spreader phenomenon gave rise to the 20/80 rule,  that 20% of the cases were responsible for 80% of the transmission of the virus (see 2011 IJID study Super-spreaders in infectious diseases)

 

Last year, for the 10 year anniversary of the SARS epidemic, the CDC authored a review of the outbreak called Remembering SARS: A Deadly Puzzle and the Efforts to Solve It.   While the whole article is a good read, I’ve lifted some excerpts from the section entitled: Solving the Mystery of “Super Spreaders”.

In the 2003 outbreak, in some instances outside the United States, a single SARS patient infected large numbers of people. At the same time, other patients did not infect people who came in contact with them. 

Researchers found that the virus was typically spread from person to person by large droplets (less efficient spread because it would be too big to linger in the air); however, at other times, clusters of illness suggested aerosol spread (where the virus can linger in the air longer after an ill person coughs) causing more spread of infections from a single sick person. 

CDC investigated the so-called “super spreaders.” They wanted to know if there were differences in when and for how long people ill with SARS might shed the virus, making them contagious to others. In the past, super spreaders had been documented during other disease outbreaks such as rubella, tuberculosis and Ebola. A common feature of super spreaders was that hospitals served as a source for the disease to widely infect others.

 

Last summer, in Branswell:The NEJM Saudi MERS-CoV Cluster Report, we looked at a review of the  hospital associated cluster involving 23 cases in the Al-Hasa region, occurring between April 1st and May 23rd. 

 

Helen Branswell’s report, which is still online, discussed the `super spreader’ angle.

 

Saudi MERS outbreak showed SARS-like features, including possible superspreader

Helen Branswell, The Canadian Press Jun 19, 2013 05:00:17 PM

TORONTO – A long-awaited report on a large and possibly still ongoing outbreak of MERS coronavirus in Saudi Arabia reveals the virus spreads easily within hospitals, at one point passing in a person-to-person chain that encompassed at least five generations of spread.

The study, co-written by Toronto SARS expert Dr. Allison McGeer, also hints there may have been a superspreader in this outbreak, with one person infecting at least seven others.

(Continue . . . )

 

As was common with SARS, and featured in the Al-Hasa report above, we are once again seeing the familiar pattern of unusually large clusters centered around health care facilities. 

 

Whether they signify an evolutionary change in the virus, the effects of `super spreaders’, or a combination of both  - or perhaps some other dynamic - is impossible to tell at this point.

 

All we can say right now is that the pattern of disease spread appears – at least temporarily, and in these two locations - to have changed in recent weeks, and that it bears watching.

 

As Dr. Osterholm said yesterday, we are definitely in a `stay tuned’ moment.

Saudi MOH Announces 7 New MERS Cases In Jeddah

 

 

# 8486

 

The Saudi MOH has just posted an update listing 7 more cases in the Jeddah Cluster.  Four are listed in stable condition, two in intensive care, and one has died.  One of the stable cases is described as a health care worker.

Based on FluTracker’s MERS Line Listing, this brings the total number of cases announced by the MOH in this Jeddah cluster to 45, over the past 3 weeks.

 

 

Health: Registration 7 cases of HIV (Corona) new in Jeddah

06/17/1435

In the context of the work of epidemiological investigation and ongoing follow-up carried out by the Ministry of Health for the virus, "Corona" that causes respiratory syndrome Middle East MERS CoV Ministry announces the registration of seven cases of HIV infection in Jeddah.

The first citizen at the age of 72 years old has passed away, Ngmayora he rest in peace.

The second citizen at the age of 70 years and receiving treatment for intensive care. God asking him a speedy recovery.

The third citizen at the age of 60 years, and intensive care receiving treatment. God asking him a speedy recovery. 

The fourth resident works the domain of health and at the age of 54 years and his condition is stable.

The fifth citizen at the age of 63 years old and in stable condition.

And sixth for citizenship at the age of 40 years old and in stable condition.

The seventh resident aged 31 years old and in stable condition.

Have been checked 180 samples have demonstrated passivity except as stated above.

Xinhua News: More Details On Zhejiang Family H7N9 Cluster

Zhejiang Province – Credit Wikipedia

 

 

# 8244

 

Via Xinhua News we’ve the first real details on the Zhejiang family cluster I reported on early this morning (see  Zhejiang Investigating Family Cluster Of H7N9 Cases).

 

Perhaps the most significant details surround the onset dates, with the father falling ill, and being confirmed infected on January 20th, while his daughter fell ill three days later.  

 

The mother was confirmed infected on the 27th, a full week after the father.

 

While a common environmental source for infection is certainly possible, this timeline would also be consistent with human-to-human transmission as well.

 

 

Chinese family of three infected with H7N9

English.news.cn   2014-01-29 21:29:49
 

HANGZHOU, Jan. 29 (Xinhua) -- Chinese health authorities on Wednesday disclosed details of a family of three who were infected with the H7N9 bird flu in east China's Zhejiang Province.

A 49-old-man surnamed Yu from Hangzhou City was confirmed on Jan. 20 to have been infected with the bird flu virus. His 23-year-old daughter, who accompanied him at the hospital, was confirmed to have caught the flu three days later, according to the provincial health and family planning commission.

Yu's wife, who also accompanied him, was confirmed to have caught the virus on Jan. 27, according to the commission.

Yu has died. His daughter is in serious condition and his wife is slightly ill.

Experts so far have no final conclusion on how the virus spread among family members. Some think they all had contact with poultry, and others think the father transmitted the flu to his wife and daughter.

Even if the case is confirmed to be a person-to-person transmission, there is no need to panic, said Li Lanjuan, an academician at the Chinese Academy of Engineering and a specialist in H7N9 prevention.

"So far there have not been any cases in which one person transmits the flu to another, and the latter transmits the virus to a third person," said Li.

In this year's epidemic, the transmission has been limited to a second person, who does not transmit the virus to a third. The H7N9 bird flu is not likely to spread in schools, workplaces or gatherings, said Chen Zhiping, deputy head of the provincial disease control and prevention center.

The probability of continuous person-to-person transmission is very slim, said Feng Zijian, deputy head of the Chinese Center for Disease Control and Prevention.

Three new human H7N9 cases were reported in Zhejiang on Wednesday, bringing the number of infections in the province this year to 56, according to the commission.

Live poultry trading has been halted in the cities of Hangzhou, Ningbo and Jinhua in Zhejiang, which has reported the most human H7N9 cases of any province. The province has launched emergency surveillance of poultry farms, parks, and migratory bird habitats, and has halted the flying of domestic pigeons.

 

 

As stated above, a family cluster – even if transmission between these three is confirmed – isn’t a game changer.

 

We’ve seen other instances of H7N9 transmission between family members (see BMJ: `Probable Person-to-Person Transmission’ Of H7N9), just as we’ve seen limited transmission of the H5N1 virus.

Should we begin to see a large number of family clusters, however, that would suggest a change in the behavior of the virus.  Which is why we monitor and scrutinize these case reports so carefully.

Zhejiang Investigating Family Cluster Of H7N9 Cases

Zhejiang Province – Credit Wikipedia

# 8239

 

 

We’ve a terse statement from the Zhejiang Ministry of Health this morning announcing their investigation into a family cluster of H7N9 cases.  Details are scant at this time, but what we know is 3 members of a family in Hangzhou all contracted the virus. 

 

Whether this was due to a common environmental exposure, or human-to-human transmission is unknown at this time.  

 

As we’ve discussed before, when it comes to proving human-to-human (H-2-H) transmission of an emerging virus, the bar is set pretty high.  When there are other, equally plausible explanations (e.g. shared environmental, or live bird exposures), then H-2-H cannot be assumed.

 

Since we’ve seen suspected limited  H-2-H transmission of the H7N9 virus in the past (see BMJ: `Probable Person-to-Person Transmission’ Of H7N9), another occurrence – while of epidemiological interest - wouldn’t be a game changer.  We take notice primarily because it could be the first visible step in a chain of transmission.

 

First the (machine translated) statement, then I’ll be back with a bit more.

 

Hangzhou together on the progress of the investigation of human infection of avian influenza H7N9 cases in family aggregation

Release date :2014-01-29

January of this year, I appointed people infected with H7N9 reported confirmed cases of avian influenza have occurred in Xiaoshan District, a family clusters of cases, three people sick. In three patients before the onset of the existence of a common environmental exposure, there are close contacts, the exact cause of the infection, the national and provincial experts are studying, one has the final official results announced immediately to the public.

 

Additional reportage indicates this cluster consists of a couple and their daughter.  This from AFP news.

 

Three H7N9 cases in same Chinese family: Xinhua

January 29, 2014 12:53 pm

SHANGHAI - Three members of the same Chinese family have contracted H7N9 bird flu in the province worst-affected by the current spike in cases, the official Xinhua news agency reported. A couple and their daughter in Hangzhou, the capital of the eastern province of Zhejiang, were infected one after another, Xinhua said late Tuesday, without giving further details.

(Continue . . .)

 

 

In 2006, we saw large clusters of H5N1 infection in both Indonesia and Turkey, and yet, it never managed to gain enough momentum to spark a pandemic (see 2006 Karo Cluster Involved H2H Transmission).  Similarly, a family cluster in Pakistan in 2007 raised concerns, but once again failed to catch fire (see EID Journal: Unraveling Pakistan’s H5N1 Outbreak).

 

Should we begin to see evidence of efficient and sustained H-2-H transmission (ie. 3rd, 4th, 5th generation transmission) - then things begin to get more interesting. 

 

But for now, we’ve no indications of that happening.

Additional Details On Zhejiang H7N9 Cluster

Zhejiang Province – Credit Wikipedia

 

# 8050

 

Although I’ve yet to see it confirmed via official government channels, local media (including Xinhuanet) are reporting that yesterday’s newly reported H7N9 infection (see Media Reports: New H7N9 Case in Hong Kong & Zhejiang Province) – a 30 year-old male – is a relative of the 57 year-old male hospitalized last week with the virus (see China: Zhejiang Province Reports H7N9 Case). 

 

Whenever we see two or more avian flu infections in close proximity, the question of human-to-human transmission comes up.   

 

As we’ve discussed before, when it comes to proving human-to-human (H-2-H) transmission of an emerging virus, the bar is set pretty high.  When there are other, equally plausible explanations (e.g. shared environmental, or live bird exposures), then H-2-H cannot be assumed.

 

Since we’ve seen suspected limited  H-2-H transmission of the H7N9 virus in the past (see BMJ: `Probable Person-to-Person Transmission’ Of H7N9), another instance – while of epidemiological interest - wouldn’t be a game changer.  We take notice primarily because it could be the first visible step in a chain of transmission.

 

Should we begin to see evidence of efficient ongoing H-2-H transmission (ie. 3rd, 4th, 5th generation transmission) - then things begin to get more interesting.  But even then, it wouldn’t necessarily signal the start of a major epidemic.  

 

In 2006, we saw large clusters of H5N1 infection in both Indonesia and Turkey, and yet, it never managed to gain enough momentum to spark a pandemic (see 2006 Karo Cluster Involved H2H Transmission).  Similarly, a family cluster in Pakistan in 2007 raised concerns, but once again failed to catch fire (see EID Journal: Unraveling Pakistan’s H5N1 Outbreak).

 

Here then, via Xinhuanet, is the latest on the Zhejiang cluster.

 

Added 1 new case of human infection in Zhejiang Province H7N9 avian influenza

December 07, 2013 Source: qianjiang evening news

Inform the PRC Zhejiang Provincial Health Department on December 6, 1 new cases of human infection in Zhejiang Province H7N9 avian flu cases . At risk patients, male, 30 years old. On December 5 confirmed, first affiliated hospital of Zhejiang University School of medicine now.

 

This reporter learned that, the infection H7N9 avian flu virus risk, was in a hospital of Zhejiang University last Wednesday the 57 confirmed Mr Chang's son-in-law.

 

So far, Zhejiang H7N9 avian flu infections increased from 4 in the second half, including jiaxing H7N9 avian flu patients died.

 

Currently, Zhang Yu and father-in-law, lived in a hospital infectious diseases Department of Zhejiang University in isolation wards. Most H7N9 avian flu patients admitted to the ward first half of the year.

 

Zhejiang and a Deputy Director of the infectious diseases Department LEUNG Wai Fung, told reporters last week confirmed a critical condition, is still in the rescue.

 

Last week, Mr fever, pneumonia, home to Zhejiang Anji register for emergency treatment, treatment process, sudden illness, respiratory failure. Were confirmed infected H7N9 avian flu.

 

Relatives told doctors, 6 chickens raised at home, before the disease is usually fed chickens, cleaning the chicken manure. Doctors speculated that Zhang H7N9 avian flu infection, most likely related to these birds carry the virus. Mr CHEUNG was diagnosed shortly after their son-in-law Mr danger symptoms of high fevers. After the examination, the throat swab H7N9 virus were positive, at present, Mr Yu accepted, including antiviral "four against two balancing" treatment, his condition is stable, conscious, do not need the help of ventilators and other equipment assisted breathing.

 

Father-in-law both continuous H7N9 avian influenza viruses, two were exposed to infected poultry, or "person to person" results? Yesterday, after the expert consultation, still do not prove that the two are "person-to-person" infection.

Our correspondent Wang Rui

 

 

The `fitness’ of the H7N9 virus for human (or at least mammalian) hosts has been the subject of a good deal of research and debate over the past 6 months, with conflicting results.  Two days ago we saw research (see TSRI: H7N9 Virus Still Binds Preferentially to Avian Receptors) suggesting that the virus (at least samples taken last spring) isn’t ready for prime time, while other studies (see mBio: H7N9 Naturally Adapted For Efficient Growth in Human Lung Tissue) are less sanguine.

 

Whatever the case (and with influenza viruses, that status can change quickly), thus far we’ve only seen widely scattered, sporadic human infections and a handful of small family clusters in the wild.  The big unknown is the prevalence and significance of mild, or asymptomatic infections, and there we can only guess.

So we watch cases like the ones this week in Hong Kong and Zhejiang province closely, for any signs that this pattern is changing.

 

The good news, so far, is that we haven’t seen compelling evidence that it has.

Updating The UAE MERS-CoV Family Cluster

 

UAE’s Proximity to Saudi Arabia

 

# 8022

 

Arabic media sources are carrying brief updates on the family cluster (husband, wife, and child) diagnosed with the MERS coronavirus this afternoon, and from the reading it appears the child is experiencing mild symptoms and was discovered during `contact testing’. 

 

The parents both appear to be suffering acute respiratory infections, and are isolated in intensive care.

 

A quick check of the  Abu Dhabi Health Authority and UAE Health Ministry websites turn up nothing `official’ on these cases.  But we’ve two translated media reports to choose from. The first from http://www.al-sharq.com.

 

UAE recorded were newly infected with "Corona" to a child Jordanian

Abu Dhabi - Agencies

UAE health authorities announced the diagnosis of new cases of HIV, "Corona" that causes respiratory syndrome Middle East for Jordanian children at the age of eight years.

According to the Health Authority in Abu Dhabi, said in a statement on Sunday, "appeared on the child's symptoms and was hospitalized simple to isolate and follow-up of the health situation."

She said that the child's parents were wounded disease was discovered a few days ago and injuries to the child tests conducted precautionary Mkhaltth virtue of his parents turned out to viral infections.

She said the Health Authority that they coordinate with the Ministry of Health and health authorities and the concerned authorities in the UAE in this regard and has taken the necessary measures and precautions in accordance with the recommendations of the scientific and conditions and criteria adopted by the World Health Organization, including epidemiological investigation of Mkhaltin.

The Health Authority of Abu Dhabi announced on Thursday the diagnosis of new cases of infection of the virus to a patient Jordanian Corona and his wife Almqaman Emirates.

 

This second report from http://www.ammonnews.net/

 

Emirates recorded new infections "Corona" to a child Jordanian

 

[12/1/2013 

Ammon - (dpa) - The health authorities of the UAE diagnosis of new cases of HIV, "Corona" that causes respiratory syndrome Middle East for Jordanian children at the age of eight years.

According to the Health Authority in Abu Dhabi, said in a statement on Sunday, "appeared on the child's symptoms and was hospitalized simple to isolate and follow-up of the health situation."

She said that the child's parents were wounded disease was discovered a few days ago and injuries to the child tests conducted precautionary Mkhaltth by virtue of his parents turned out having the virus.

She said the Health Authority that they coordinate with the Ministry of Health and health authorities and stakeholders the UAE in this regard and has taken the necessary measures and precautions in accordance with the recommendations of the scientific and conditions and criteria adopted by the World Health Organization, including epidemiological investigation of Mkhaltin.

The Health Authority of Abu Dhabi announced on Thursday new cases diagnosed cases of HIV in a patient Jordanian Corona and his wife Almqaman Emirates.

The patient's age 38 years and is currently receiving treatment in intensive care and his wife, eight months pregnant and infected with acute respiratory symptoms and receiving treatment in intensive care at a hospital in the UAE.

 

Updating The Dothan, Alabama Respiratory Cluster Story

 

Dothan, Ala Perry-Castañeda Library Map Collection

 

UPDATED -  See  Alabama Health Alert Message On Respiratory Cluster

 

# 7308

 

While we don’t have an answer yet of the cause of a small geographically linked cluster of unidentified respiratory illnesses in southeast Alabama (see Press Conference On Dothan, Alabama Respiratory Cluster), we do have another video news report from a local TV station that provides us with a few more details.

 

 

(Click Image to watch 2 minute Newscast)

 

WFSA-TV reports that the cases all involve adults (age range from early 20’s to late 80s), and they were all admitted to the Southeast Alabama Medical Center starting last Thursday.

 

Two patients have died (reported by other media as over the weekend), and samples are being tested by the CDC.

 

I’ve not been able to locate the `letter’ to doctors the newscast describes, any announcement on the the SAMC webpage, or any HAN (Health Alert Network) message from the state or CDC regarding this case (updated Aabama Health Alert Message On Respiratory Cluster).

 

Hopefully we’ll get some clarity over the cause from the lab tests sometime today.

NEJM: Community Cluster Of Tamiflu Resistant H1N1

 

 

# 4142

 

Today the NEJM has published a letter from investigators in Vietnam that outlines the community transmission of a `fit’ oseltamivir (Tamiflu) resistant strain of the pandemic H1N1 virus.

While several dozen cases of Tamiflu resistant novel H1N1 have been reported, up until very recently we mostly heard about single cases of presumably `spontaneous’ mutations that occurred in patients taking the antiviral.

 

Oseltamivir (Tamiflu) Resistance is associated with the swapping of the amino acid histidine for tyrosine  at position 275 (N1 numbering) in the neuraminidase glycoprotein (H275Y).

 

Up until a couple of years ago, it was assumed that this mutation reduced the transmissibility, or biological fitness of the virus.

 

That theory evaporated when resistant seasonal H1N1 began to circulate widely in 2008.

 

Efficient transmission of resistant novel H1N1, with the exception of two clusters among immunocompromised patients in hospitals, had not been established.

 

Until today.

 

Helen Branswell has the details, and I’ve a link to the correspondence published today in the NEJM (New England Journal of Medicine).

 

As with any Branswell story, follow the link to read it in its entirety.

 

Transmission of Tamiflu-resistant H1N1 on a Vietnamese train 'a concern': WHO

By: Helen Branswell, Medical Reporter, THE CANADIAN PRESS

9/12/2009

TORONTO - Seven healthy people on a train from Ho Chi Minh City to Hanoi in Vietnam caught Tamiflu-resistant H1N1 flu, researchers reported Wednesday in a prominent medical journal.

 

The transmission event, which occurred in July, is one of the largest clusters of cases of resistant H1N1 seen so far and the first time so many linked cases have been seen in previously healthy people who had not been on the drug.

 

Surveillance since the summer has only turned up three additional drug resistant viruses, the authors note in their letter to the New England Journal of Medicine. But they say they cannot rule out the possibility of ongoing transmission of resistant pandemic H1N1.

 

The event is a warning that resistant viruses can spread among healthy people and more such events may be in store, an antiviral expert with the World Health Organization said.

(Continue . . . )

 

The the link to the NEJM letter, along with the opening paragraphs.

 

Published at www.nejm.org December 9, 2009 (10.1056/NEJMc0910448)

A Community Cluster of Oseltamivir-Resistant Cases of 2009 H1N1 Influenza

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.

(Continue .  .  .  )

 

It should be noted that for now, at least, Tamiflu remains effective for the vast majority of novel H1N1 infections around the world.  We don’t yet know if the novel H1N1 virus will follow its seasonal cousin’s lead, and eventually become widely resistant.

 

And even if that happens, we don’t know how long it would take. 

 

Presumably months, anyway.

 

So yes, this is a `concern’.  At least in the long run.  

 

Antivirals were always assumed to be a temporary stop-gap measure during a pandemic.   Not only are the supplies of antivirals limited, resistant viruses were predicted to evolve over time. So reports such as this one are not unexpected.

 

That is why the focus has been so heavily on vaccines.

 

While Tamiflu may continue to be useful for months or possibly even years to come, preventing an infection is always preferable to treating one.

 

The potential loss of treatment options over time is another factor to seriously consider when deciding whether to take the H1N1 vaccine.