EID Journal: Extensively Drug Resistant NDM Bacteria In The Environment – Dhaka, 2012

E. coli – Photo Credit CDC

 

# 9994

 

It’s been nearly 5 years since The Lancet published a study (see NDM-1: A New Acronym To Memorize)  by Walsh, Toleman, Livermore, et al. that awakened the world to the emergence and growing prevalence of the NDM-1 (New Delhi metallo-β-lactamase) enzyme that can make many types of bacteria resistant to a wide spectrum of antibiotics - including Carbapenems.

 

Carbapenems are newer generation beta-lactam antibiotics (a class that includes penicillins, cephalosporins, cephamycins, and carbapenems) that are usually reserved as an antibiotic of last resort.

 

Complicating matters, this enzyme is carried by a plasmid – a snippet of portable DNA  - that can be transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species) in a shared environment. 

In 2011 (see Lancet Study: NDM-1 In New Delhi Water Supply), Timothy Walsh, Janis Weeks, David M Livermore, and Mark A Toleman  published a study that looked for – and found – bacteria carrying the NDM-1 enzyme in New Delhi's drinking water supply.

 

A snippet from the press release stated ominously (emphasis mine):

 

Resistant bacteria were found in 4 per cent of the water supplies and 30 per cent of the seepage sites. The researchers identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.

 

In an interview for Reuters, co-author Mark Toleman of Britain’s Cardiff University School of Medicine stated that as many as 500,000 residents of New Delhi may be carrying the NDM-1 resistance gene in their gut flora. Like with MRSA, carriage of NDM  bacteria does not necessarily mean infection, and even asymptomatic carriers can still spread it to contacts and to the environment.

 

Since then, scattered variants of NDM-1 have begun to emerge (see First Imported Case Of NDM-4 Reported In Hong Kong) around the globe, often in travelers recently returned from the Indian Subcontinent (see VOA News  report  Concerns Mount Over India's Role In Incubating Drug-Resistant Bacteria).

 

India’s response to all of this negative publicity was initially angry denial, but in 2014 – bowing to immense international pressure – India introduced new regulations designed to halt the unregulated sale of more than 3 dozen cheap and powerful (Schedule H1) antibiotics.

 

Recent media reports (see 515 chemists lose licences in Pune div) suggest less than full compliance, so it is difficult to know how much of an impact these laws are having.

 

Last year, in EID Journal: Acquisition of Drug Resistant Genes Through International Travel, we looked at a study from the Netherlands tested that 122 healthy travelers both before and after making an international trip for evidence that they carried one of (several) antimicrobial resistance-inducing genes.

 

They found a high rate of resistance genes in the commensal gut bacteria of returning travelers – particularly those visiting Southeast Asia and the Indian subcontinent .

 

All of which serves a prelude to a new Dispatch in the EID Journal  – again from Dr. Toleman et al.  - that looked for, and found, NDM encoding bacteria prevalent in the Dhaka’s environment.  They also found evidence - that while rife today - this carbapenemase is a relatively recent arrival to Bangladesh.

 

I’ve only excerpted the abstract and conclusions, so follow the link to read this report in it its entirety.

 

Dispatch

Extensively Drug-Resistant New Delhi Metallo-β-Lactamase–Encoding Bacteria in the Environment, Dhaka, Bangladesh, 2012

Mark A. Toleman , Joachim J. Bugert, and Syed A. Nizam

Abstract

Carriage of the New Delhi metallo-β-lactamase variant 1 (NDM-1) enables drug resistance to move between communities and hospitals. In Bangladesh, we found the bla_NDM-1 gene in 62% of environmental waters and in fermentative and nonfermentative gram-negative bacteria. Escherichia coli sequence type (ST) 101 was most commonly found, reflecting a common global relationship between ST101 and NDM-1.

<SNIP>

Conclusions

Our findings indicate that NDM-1 is widespread in the Dhaka environment. We detected 241 NDM-1–encoding bacterial isolates; they were found in all 7 sampled regions and at 36 (62%) of the 58 sampling sites. This high level of environmental bla_NDM-1 contamination is of concern, especially because drinking water in Bangladesh usually carries high levels of sewage-derived bacteria (11). It is therefore likely that bla_NDM-1 carriage rates will rise rapidly. Future environmental studies could provide indicators of epidemics of emerging resistant bacteria before they are realized in hospitals.

Despite the widespread presence of NDM-1 in Dhaka, it appears that this carbapenemase has recently emerged in the Bangladesh environment. Studies in northern Bangladesh did not find NDM-1 in wild ducks and poultry in 2009 (9) or in crow and gull feces in 2010 (10). Similarly, NDM-1 was not detected in drinking water in Dhaka during 2008–2009 (11) even though all samples had high levels of fecal and bla_CTX-M-15 contamination. Furthermore, a study of 1,879 clinical E. coli and Shigella spp. isolates collected during 2009–2010 in Bangladesh did not detect bla_NDM-1 (12). The first known clinical isolates date from 2008 (12), and the first evidence of human gut carriage of bla_NDM-1 was found in samples collected in Dhaka (13) a month before our study.

Because E. coli is the leading cause of human urinary tract infections, bloodstream infections, and neonatal meningitis, the ability of NDM-1 to give this bacterium clinical resistance to carbapenems is of concern (14). E. coli is also universally carried in the human gut. Therefore, we focused on this species because it is likely to be the greatest threat to human health. E. coli encoding NDM-1 were found in 3 of the 7 sampled regions, and genotyping showed they belonged to only 3 STs: ST648, ST101, and ST405. These same 3 E. coli genotypes are responsible for 80% of clinical NDM-1–encoding E. coli isolates in the United Kingdom (15). Furthermore, ST101 is the most common E. coli genotype in the Bangladesh environment (10.3% prevalence) and in clinical isolates from the United Kingdom (50%). Results of a literature search for NDM-1–encoding E. coli belonging to ST101 showed that this genotype has been detected in 15 nations (Figure 2). Thus, E. coli ST101 appears to be a successful global genotype that is often associated with NDM-1. This association with a single global genotype is analogous to the association between E. coli ST131 and the cephalosporinase CTX-M-15. Because of the critical nature of extensively drug-resistant bacteria, we are investigating the underlying factors responsible for the success of these particular antimicrobial drug–resistant strains

 

While still relatively rare – at least in the United States and Europe – this ever expanding 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 year later CDC Director Thomas Frieden called it a `nightmare bacteria’ during the release of a major US report on the threat (see MMWR Vital Signs: Carbapenem-Resistant Enterobacteriaceae (CRE)).

 

For more on the growing threat of antibiotic resistant bacteria, you may wish to revisit:

 

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’

Bangladesh Reports Imported MERS Case

 

 

• Traveler likely contracted the virus in Abu Dhabi

 

# 8745

 

Although details are still sketchy, and I find no official mention on the Bangladesh’s IEDCR website, there are widespread media reports this morning (Reuters, Daily Star, Bangladesh News Service) announcing that country’s first imported MERS case. 

 

The most complete coverage I can find comes from BDNews24.com:

 

 

 

First case of MERS in Bangladesh

Nurul Islam Hasib,  bdnews24.com

Published: 2014-06-15 13:29:30.0

Bangladesh has confirmed the first case of the deadly Middle East Respiratory Syndrome coronavirus (MERS) after a 53-year-old man returning from the US via Abu Dhabi was found afflicted with it.

Prof Mahmudur Rahman, director of the national disease control agency, IEDCR, said the man was recuperating in a hospital.

“We have notified it to the WHO,” he told bdnews24.com on Sunday.

<SNIP>

Prof Rahman, also a WHO expert on the board reviewing MERS, warned against unnecessary panic .

He said the virus has not spread further within the country after it has come here from the Middle East.

“We urge everyone to report to the hospital if they fall sick after returning from particularly abroad”.

The first case was detected on Sunday. The 53-year-old man had returned Dhaka on June 4.

Symptoms showed up on June 6 and the person landed up in a hospital on June 9 with severe breathlessness.

The IEDCR director said they had made hospitals aware of the disease so that they report them if a suspect patient was found.

“We have tested 39 suspects, but only has tested positive so far,” Rahman said.

(Continue . . .)

Another report, albeit with fewer details, this time from Reuters:

 

Bangladesh reports first case of MERS infection

DHAKA Sun Jun 15, 2014 5:48am EDT

 (Reuters) - Bangladesh on Sunday reported its first case of Middle East Respiratory Syndrome (MERS) coronavirus infection in a man returning from the United States through Abu Dhabi.

The man, 53, was being treated in hospital, said Mahmudur Rahman, of the Institute of Epidemiology, Disease Control and Research.

"Most probably, he contacted the virus while he was in Abu Dhabi in transit on his way back from the United States," Rahman told Reuters.

(Continue . . .)

 

Unless I’ve missed a country, this should bring to 22, the number of nations that have now reported at least 1 MERS Case.

IEDCR Reports H5N1 Fatality In Bangladesh

 

# 7091

 

 

While our attention is understandably focused on the emerging H7N9 virus in China, the H5N1 virus continues to circulate in birds, and occasionally infect humans, as well.

 

Earlier this week we learned of a new Cambodian infection (see Meanwhile, Cambodia Reports Their 10th H5N1 Case) and today, Bangladesh’s IEDCR reports on a toddler who died in February, but was just now diagnosed as having the virus.

 

While Bangladesh has reported six previous H5N1 cases, quite unusually, all were relatively mild and all survived. This becomes Bangladesh’s first known bird flu fatality.  A hat tip to Giuseppe Michieli  and Biological on FluTrackers for posting the story.

 

 

 

Seventh H5N1 case in Bangladesh

The seventh case of Influenza A (H5N1) has been confirmed from one of our surveillance sites. Diagnosis was made on the basis of Real time RT-PCR.

 

This was a 1 year 11 months old male child from Chauddogram, Comilla. He was admitted to Comilla Medical College Hospital, later transferred to Dhaka Shishu Hospital and then to a private clinic. He died on 18th February, 2013. This is the first death case of H5N1 in Bangladesh. As this child had no typical features of Influenza Like Illness (ILI), throat and nasal samples were sent for reconfirmation to CDC Atlanta, USA (WHO reference laboratory) and received confirmation on 6th April, 2013.

 

Detailed outbreak investigation was conducted. There was strong epidemiological link with backyard poultry deaths. No other case was found among contacts during the investigation.

Bangladesh: Nipah Update

WHO Nipah Virus (NiV) Infection GAR page

Photo by Chi Liu 

 

# 6999

 

For many infectious disease watchers, Nipah virus (NIV) holds a certain fascination. Identified only 14 years ago, this bat-borne virus produces deadly, albeit small, outbreaks of disease each year between December and May in Bangladesh.

 

The primary route of infection in Bangladesh is linked to the consumption of of raw (uncooked) date palm juice - which is `tapped’ from cuts in trees much in the same way as maple trees are for their syrup.

Date Palm Sap Collection – Credit FAO

 

But human-to-human transmission has been reported as well, along with infection from intermediate hosts.

 

In 1999, hundreds of abattoir workers in Malaysia and Singapore were infected from pigs carrying the virus (see MMWR Update: Outbreak of Nipah Virus -- Malaysia and Singapore, 1999) killing more than 100.

 

And once infected, humans can transmit the virus on to others, albeit not terribly efficiently (see EID Journal Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community).

 

Nipah (and its Australian cousin Hendra, discovered in 1994) are sufficiently different from other members of the Paramyxoviridae family to have led to the creation of a new genus; Henipavirus.

 

This year, we’ve been following Nipah’s progress in Bangladesh (see here and here), and today their Institute of Epidemiology Diseases Control and Research (IEDCR) has a new update.

 

As you will see, victims are predominantly male, and the CFR (Case Fatality Ratio) is nearly 90%.

 

 

Nipah Infection in 2013

Update on 12 March, 2013

Situation Update:

12 March 2013:  19 Nipah cases were identified among them 17died  (mortality rate 89%);. These cases are from 13 districts (Gaibandha, Natore, Rajshahi, Naogaon, Rajbari, Pabna, Jhenaidah, Mymensingh, Nilphamari, Chittagong, Kurigram, Kustia). Age distribution of cases are 8 months to 55 years among them 13 are male and 6 are Female.

Nipah

Human Nipah virus (NiV) infection, an emerging zoonotic disease, was first recognized in a large outbreak of 276 reported cases in Malaysia and Singapore from September 1998 through May 1999.

Agent

NiV is a highly pathogenic paramyxovirus belonging to genus Henipavirus. It is an enveloped RNA virus.

Incubation period

The median incubation period of the secondary cases who had a single exposure to Nipah case was nine days (range 6–11 days) but exposure to onset of illness varies from 6-16 days. The median incubation period following single intake of raw date palm sap to onset of illness is 7 days (range: 2-12 days) in Bangladesh.

Transmission:

1. Drinking of raw date palm sap (kancha khejurer rosh) contaminated with NiV

1. Close physical contact with Nipah infected patients

Surveillance

Nipah surveillance began in 2006, Institute of Epidemiology, Disease Control and Research (IEDCR) in collaboration with ICDDR,B established Nipah surveillance in 10 District level Government hospitals of the country where Nipah outbreaks had been identified. Presently surveillance system is functioning in five hospitals of Nipah Belt.

 

While as many as half of all Nipah infections reported in Bangladesh appear to be secondary infections (due to close contact with someone already infected) the virus has not managed to spark an epidemic. 

 

The caveat being that viruses – particularly singled-stranded RNA viruses like Nipah (along with influenzas, hantaviruses, filoviruses, and others) -are known for their ability to mutate.

 

When Steven Soderbergh made his pandemic thriller `Contagion’ a couple of years ago, technical advisor Professor Ian Lipkin created fictional MEV-1 virus based on a mutated Nipah virus (see The Scientific Plausibility of `Contagion’).

 

While the Nipah virus continues to produce only small, limited outbreaks, we watch these developments closely each year for any signs of change.

Bangladesh: Updating The Nipah Outbreak

Date Palm Sap Collection – Credit FAO

 

 

# 6904

 

 

The history of emerging infectious diseases in recent decades has increasingly implicated bats as significant reservoirs of potentially dangerous zoonotic pathogens.

 

While long known for carrying the most dreaded of viruses – rabies – during the 1990s we learned that certain types of  bats were also natural hosts of  both Nipah and Hendra, henipaviruses in the family Paramyxoviridae.

 

In recent years Marburg virus has been isolated in Egyptian Fruit bats in Kenya, and antibodies to Ebola viruses have been found in bats in both Africa and Asia (see EID Journal: Ebola Virus Antibodies From Bats In Bangladesh.

 

In 2003 the SARS epidemic – caused by a novel coronavirus which was initially linked to Civits, but later linked to bats, emerged (see EID Journal  Review of Bats and SARS).

 

In 2012, for the first time a `bat influenza virus’ was discovered (see A New Flu Comes Up To Bat), and the newly detected novel coronavirus from the Middle East - EMC/2012 – has been tentatively linked to bats as well (see EID Journal: EMC/2012–related Coronaviruses in Bats).

 

Bats are abundant, geographically widespread, and able to move over long distances – and  according to the Bat Conservation Trust - there are more than 1,000 types of bats, which make up roughly 1/5th of all mammalian species.

 

All things considered, Chiroptology (the study of bats) among infectious disease investigators has never been more in vogue.

 

Since we’ve already seen one major epidemic spring from bats – bat coronaviruses are closely monitored - but the Nipah virus, which has demonstrated a limited ability to transmit from human-to-human, keeps a lot of researchers up at night as well.

 

Since it was first identified in Malaysia in 1998, most of the outbreaks have been centered around Bangladesh.

 

Epidemiological investigations have fingered the consumption of raw (uncooked) date palm juice - which is `tapped’ from cuts in trees much in the same way as maple trees are for their syrup – as the virus’s primary route into the human population.

 

Fruit bats of the Pteropodidae family are the reservoir host for the virus, and usually carry it asymptomatically. Roosting in trees rather than caves, they can easily contaminate the date juice collection jars with their virus laden urine and feces.

 

From there the virus can jump into unwary imbibers of the beverage. But it isn’t necessarily a dead end infection for Nipah, as humans can spread the virus amongst themselves as well (see EID Journal Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community).

 

Collection of date palm juice is a seasonal activity (December - May) in Bangladesh, so that time period also defines their Nipah season as well.

 

Last Sunday, in Bangladesh: Nipah Returns, we looked at a fresh outbreak that had infected 8, and killed 6 in recent weeks. 

 

Today, an update from Bangladesh’s Institute of Epidemiology Diseases Control and Research (IEDCR) which raises the total number of infections (as of Jan 30th) to 11, with 8 deaths.

 

Update on 30 January, 2013

Situation Update:

30^th January 2013:  11 Nipah cases were identified among them 8 died  (mortality rate 73%); 3 cases are still under treatment. These cases are from 8 districts (Gaibandha, Natore, Rajshahi, Naogaon, Rajbari, Pabna, Jhenaidah, Mymensingh). Age distribution of cases are 8 months to 43 years among them 8 are male.

 

Till January 30, 2013, a total of 176 human cases of Nipah infection in Bangladesh were recognized from outbreak among them 136 (77%) died.

Nipah

Human Nipah virus (NiV) infection, an emerging zoonotic disease, was first recognized in a large outbreak of 276 reported cases in Malaysia and Singapore from September 1998 through May 1999.

Agent

NiV is a highly pathogenic paramyxovirus belonging

to genus Henipavirus. It is an enveloped RNA virus.

Incubation period

The median incubation period of the secondary cases who had a single exposure to Nipah case was nine days (range 6–11 days) but exposure to onset of illness varies from 6-16 days. The median incubation period following single intake of raw date palm sap to onset of illness is 7 days (range: 2-12 days) in Bangladesh.

Transmission:

1. Drinking of raw date palm sap (kancha khejurer rosh) contaminated with NiV

1. Close physical contact with Nipah infected patients

Surveillance

Nipah surveillance began in 2006, Institute of Epidemiology, Disease Control and Research (IEDCR) in collaboration with ICDDR,B established Nipah surveillance in 10 District level Government hospitals of the country where Nipah outbreaks had been identified. Presently surveillance system is functioning in five hospitals of Nipah Belt.

 

 

So far, while roughly half of all Nipah infections in Bangladesh appear to be secondary infections (due to close contact with someone already infected) the virus has not managed to spark an epidemic. 

 

But viruses – particularly singled-stranded RNA viruses like Nipah (along with influenzas, hantaviruses, filoviruses, and others) can mutate at exceptionally high rates, and so what we can say is true about them today may not hold true tomorrow.

 

For more on  bats, and bat-hosted viruses, you may wish to revisit:

 

Disease Transmission At The Human-Animal Interface

Coronavirus `Closely Related’ To HK Bat Strains

Virology Journal: Ebola Virus In Chinese Bats

Bangladesh: Updating Nipah & The CDC Director’s Visit

Credit – The CDC’s GDDER

# 6888

 

I wrote at length yesterday on the Nipah virus, and the current outbreak in Bangladesh (see Bangladesh: Nipah Returns, so I’ll not bother repeating those points this morning. 

 

What is new this morning is a report from Xinhua News indicating that three more Nipah cases (two fatal) have been reported in Bangladesh, and the arrival on Saturday of U.S. CDC Director Thomas Frieden in Dhaka to discuss their plans to assist that nation in strengthening disease surveillance.

 

First the report from Xinhua on the latest Nipah cases.

 

Virus Nipah strikes back in Bangladesh, claims 8 more lives within one week

2013-01-28 10:00:41 GMT2013-01-28 18:00:41(Beijing Time) by Naim-Ul-Karim

 

DHAKA, Jan. 28 (Xinhua) -- Bangladesh on Monday reported eight more deaths from infection with the deadly Nipah virus within one week as the bat-borne disease has struck early and hard.

 

The country's Institute of Epidemiology, Disease Control & Research (IEDCR) confirmed two more deaths Sunday from the Nipah infection, tallying the toll at eight from Jan. 22.

 

"Outbreak of the deadly Nipah virus has claimed eight lives since January 22," Mahmudur Raman, head of the IEDCR, told Xinhua Monday.

 

"As of today, there are 11 cases from eight Bangladesh districts including Dhaka and eight of them died," he said, adding "Three Nipah-infected patients remain critically ill."

(Continue . . .)

 

The Institute of Epidemiology, Disease Control and Research (IEDCR) in Bangladesh has far more to deal with than just the Nipah virus. The 150+ million inhabitants of Bangladesh are also subject to H5N1 bird flu, Dengue, Anthrax, and Chikungunya, along with many other diseases.

 

The United States has been providing ongoing technical, financial, and logistical support to Bangladesh for several years to assist them in upgrading their disease detection and surveillance systems.  Hence the visit this past weekend by the CDC’s Director.

The news site BDNews24 has details of Director Frieden’s 2-day visit.  Follow the link to read:

 

 

Bangladesh to be 'Global Disease Detection site'

Senior Correspondent,  bdnews24.com

Published: 2013-01-27 14:56:52.0 Updated: 2013-01-27 18:24:00.0

The US Centres for Disease Control and Prevention (CDC) is strengthening its ties with Bangladesh as part of its initiative to protect the global community from the urgent public health threats.

(Continue . . . )

 

 

Improving disease surveillance, detection, and prevention in those regions where emerging diseases are most apt to occur is not only the humanitarian thing to do, it also helps to keep the world from being blind-sided by emerging infectious disease threats.

 

We’ve far too many `blind spots’ around the world where a novel virus could emerge, and take hold in the population, before it could be identified and (hopefully) contained.

 

To counter that threat, the CDC has developed a Global Disease Detection and Response division (GDDER).

 

 

Global Health - Global Disease Detection and Emergency Response

The Division of Global Disease Detection and Emergency Response (GDDER) protects Americans and the global community from urgent public health threats and provides public health relief for humanitarian emergencies. Activities include:

• Detecting and containing emerging health threats
• Deploying CDC experts 24 hours a day, 7 days a week at host country requests for technical assistance and other support
• Building capacity by providing technical assistance in support of International Health Regulations (IHR)
• Promoting policies for public health and bio-security
• Improving the health of populations affected by complex humanitarian emergencies.

 

According to the GDDER website, nations are selected by the following criteria:

 

• Public health significance: The country has a high population density or history of infectious diseases or expected potential for emerging diseases;
• Country commitment: The country supports and values partnership with CDC and will actively engage in collaborative activities and identify new partners;
• Established CDC presence: The country has an established, effective working relationship with CDC and supports CDC staff in-country;
• Established regional reach: The country has the infrastructure and regional stature to serve as regional resource, or is already acting as a regional leader in other arenas;
• International partner presence: The country has other U.S. Government agencies and international partners operating in-country.

The GDDER is a program that will hopefully not only help alert us of an emerging infectious disease threat, but that may also provide a chance to stop it in its tracks before it can spread.

While there are no guarantees of success, this is a public health advantage that previous generations could only have dreamed of.

EID Journal: Ebola Virus Antibodies From Bats In Bangladesh

Common pipistrelle (Pipistrellus pipistrellus) – Credit Wikipedia

# 6861

 

 

Several months ago in a blog called Virology Journal: Ebola Virus In Chinese Bats, we looked at the first evidence suggesting that Ebola viruses are circulating among bats in China, although the exact strain involved wasn’t clear.

 

Researchers were able to detect cross-reactive antibodies to two types of Ebola viruses (Zaire and Reston), but identification of the exact EBOV strain in China was not possible.

 

The natural reservoir for Ebola viruses are believed to be fruit bats of the Pteropodidae family, although the virus in humans is usually linked to the consumption of infected bushmeat (considered an intermediate host).

 

There are currently five known strains of the Ebola virus - Ebola-Zaire, Ebola-Sudan, Ebola-Reston, Ebola-Ivory Coast and Ebola-Bundibugyo – which along with a close cousin - the Marburg virus - make up the family Filoviridae.

 

Of these, only Ebola-Reston – found primarily in the Philippines – does not cause illness in humans.

 

Up until recently, Ebola Reston was the only ebolavirus thought to circulate outside of Africa.

 

Today, the CDC’s EID JOURNAL published a Dispatch that describes the seroprevalence of cross reactive antibodies against Ebola in bats tested in Bangladesh. A few excerpts, but follow the link to read the dispatch in its entirety.

 

Volume 19, Number 2—February 2013

Dispatch

Ebola Virus Antibodies in Fruit Bats, Bangladesh

Kevin J. Olival , Ariful Islam, Meng Yu, Simon J. Anthony, Jonathan H. Epstein, Shahneaz Ali Khan, Salah Uddin Khan, Gary Crameri, Lin-Fa Wang, W. Ian Lipkin, Stephen P. Luby, and Peter Daszak

Abstract

To determine geographic range for Ebola virus, we tested 276 bats in Bangladesh. Five (3.5%) bats were positive for antibodies against Ebola Zaire and Reston viruses; no virus was detected by PCR. These bats might be a reservoir for Ebola or Ebola-like viruses, and extend the range of filoviruses to mainland Asia.

<SNIP>

Conclusions

Our study provides evidence of Ebola virus infection in wildlife from mainland Asia and corroborates the observation that filoviruses are harbored across a much larger geographic range then assumed (2). Preferential reactivity to ZEBOV suggests exposure to an Ebola virus that is distinct from REBOV, the only filovirus currently found in Asia. We consider the likelihood of cross-reactivity with MARV as low because there is only a 35% aa identity between nucleoprotein genes of REBOV/ZEBOV and MARV. However, we cannot rule out co-infection with multiple filoviruses.

(Continue . . . )

 

An interesting side note, one of the authors listed on this dispatch is Professor Ian Lipkin, director of Columbia University’s Center for Infection and Immunity in New York. 

 

Dr. Lipkin served as technical advisor for the  2011 film Contagion, and created the fictional MEV-1 bat virus used as the movie’s viral villain  (see The Scientific Plausibility of `Contagion’).

 

Our knowledge of the diseases carried by bats has expanded considerably since the early 1990s. Up until that time, the primary concern was rabies.  

 

During the 1990s – two new bat-borne viruses emerged - Nipah and Hendra - both henipaviruses of the family Paramyxoviridae.

 

The Hendra virus was first isolated in 1994 after the deaths of 13 horses and a trainer in Hendra, a suburb of Brisbane, Australia. A stable hand, who also cared for the horses, was hospitalized, but survived.

 

Over the past 18 years 40 outbreaks of Hendra virus – all involving horses – have been reported in Australia. Four human fatalities have been linked to the virus as well.

 

 

The debut of Nipah was in Malaysia in 1998, where the virus first jumped from bats to local swine herds, probably via bat droppings into the swine’s environment or food. From there, it jumped to humans, resulting in 265 cases of acute encephalitis and more than 100 deaths (cite).

 

This first human outbreak was initially thought to be due to Japanese encephalitis, and so precautions around pigs were delayed for nearly two months, allowing the virus to spread.

 

Over the past decade, Nipah has sparked a number of small outbreaks across Southern Asia, although the most intense activity has been centered around Bangladesh.

 

Nipah/Hendra Virus & Fruit Bat Home Range – WHO

 

The most notorious of the emerging bat-viruses has been  SARS-CoV (coronavirus), which sparked an epidemic in 2002-2003 that infected roughly 8,000 people around the globe, killing nearly 800.

 

Which explains why so much interest has been paid to the detection last year of a handful of novel coronavirus infections in the Middle East (see WHO Coronavirus Update).

 

And perhaps most surprisingly of all, early in 2012 we learned about a new strain of influenza found in an unusual host: bats (see A New Flu Comes Up To Bat).

 

This discovery adds an H17 flu subtype, and a new host species, suddenly making all of the textbooks and slide presentations on influenza out of date.

 

In 2007 a PNAS article called A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans, told of a 39 year old man infected when a bat flew into their Malaysian home.  More than a week after he was placed in isolation, two other members of his family came down with the same illness, suggesting H-2-H transmission. 

 

The authors of that report wrote:

 

Bats, probably the most abundant, diverse, and geographically dispersed vertebrates on earth, have recently been shown to be the reservoir hosts of a variety of zoonotic viruses responsible for severe human disease outbreaks, some with very high mortality.

 

While most researchers expect the next pandemic to come from a swine or avian source, other species – like bats – are increasingly being looked to as significant reservoirs of dangerous zoonotic pathogens.

 

All of which makes studies, like this one today, of particular interested to researchers.

ICEID: Another H5N1 Seroprevalence Study To Ponder

 

 

# 6218

This week I hope to highlight some of the ICEID 2012 abstracts (see ICEID 2012: Abstracts & Program) of particular interest to Flublogians.

 

With the recent controversy over the seroprevalence of H5N1 virus (see Science: Peter Palese On The CFR of H5N1 & mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective) we’ve seen estimates ranging from there being relatively few undetected human cases of H5N1 infection to `millions’.

 

If there are mild or subclinical infections with the virus going undetected, the best way to find them is to look for antibodies in the blood of those who have had substantial exposure to poultry.

 

Which is precisely what researchers at International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B), Bangladesh’s Institute of Epidemiology, Disease Control and Research (IEDCR), and the CDC did.

 

They performed microneutralization assays on workers from 89 poultry farms with confirmed H5N1 outbreaks and 3 live bird markets reporting high poultry mortality to detect neutralizing antibodies in sera using A/Bangladesh/207095/2008 (H5N1).

 

The following abstract can be found on page 116 of the 2012 ICEID Abstract, I’ve just excerpted the conclusion.

 

Board 183. Sero-prevalence of H5N1 Antibodies among Poultry Workers in Bangladesh, 2008–2009

S. Nasreen, S.U. Khan, E. Azziz-Baumgartner, K. Hancock, J.M. Katz, V Veguilla, D. Wang , M. Rahman, A. Alamgir, E.S. Gurley, K. Sturm-Ramirez T.M. Uyeki , S.P. Luby

Conclusions: Despite extensive poultry
exposures, no serological evidence of H5N1 virus infection was found among farm or market poultry workers during 2008-09.

However, the recent cases of human H5N1 infection detected in Bangladesh and the continued circulation of H5N1 among poultry warrants continued surveillance among a larger cohort of poultry workers to monitor the risk of avian-to-human H5N1 virus transmission.

 

 

It should be noted that since the beginning of the year, Bangladesh has detected 3 H5N1 infections among live poultry market workers through routine surveillance (see IEDCR On The Bangladesh H5N1 Cases).

 

All appear to have had mild to moderate illness, and have recovered.

 

With multiple clades of the H5N1 virus in circulation around the world - and constantly mutating - what may have been true in 2009 may not hold true today. 

So ongoing seroprevalence studies in Bangladesh, and other regions where the virus is endemic, are sorely needed.

IEDCR On The Bangladesh H5N1 Cases

 

 

# 6198

 

Last week we learned of a the detection of the H5N1 virus in a vendor at a live bird market in Bangladesh (see Bangladesh: Reporting Their 4t/h H5N1 Case), making the 4th known case from that nation.

 

Yesterday a number of websites carried a news report (see Crofsblog Bangladesh: 3 market workers infected with H5N1 on the detection of 2 more cases. 

 

Since then, I’ve attempted to access Bangladesh’s IEDCR (Institute of Epidemiology, Disease Control & Research) to get more information, but their website has been offline until this morning.

 

While their site is running unusually slow, we now have access, and as you’ll see by the screen shot below, avian influenza is suddenly a hot topic.

 

 

The 2nd entry (Fifth and Sixth H5N1 Human Case In Bangladesh) is brief.

 

Fifth and Sixth H5N1 human case in Bangladesh

Two cases of Influenza H5N1 has been reported from the same surveillance site, as of fourth case, at live bird market in Dhaka City (South) on 04 March 2012. This was confirmed by Real time RT-PCR. It may be mentioned that they are the fifth and sixth cases of laboratory confirmed Influenza H5N1 cases of Bangladesh since the first case detected in 2008.

The fifth case is 26 year old male and sixth case is 18 year old male who had presented with history of cough. Now they are free from symptoms. Nasal and throat swab were collected and found positive for H5N1. They are also live bird market workers, like the fourth case.

They are being treated and followed up by National Rapid Response Team members from IEDCR and ICDDR,B.

 

 

They have also posted a 126-page pdf on the handling of human H5N1 cases, which unlike many of the documents on this site, is in English (not Bengali).

 

 

And lastly, a 4-page educational PDF written in Bengali – appropriately named Birdflumess.pdf.

 

 

Unlike nearly every other country that has seen H5N1 infections in humans, those detected in Bangladesh appear to have been only of mild to moderate severity, and all have recovered.

 

Leaving us with a bit of a mystery. 

Is there something different about the virus circulating in Bangladesh, or do people in that region – due to previous exposure to avian viruses – carry some level of community immunity?

Something I’m sure researchers are eager to find out.

Bangladesh: Reporting Their 4th H5N1 Case

# 6186

 

Although Bangladesh has seen a great deal of H5N1 in poultry over the past 4 years, they have – until now – only reported 3 human infections with the avian flu virus. The first case was detected in 2008, while two additional cases were found in 2011.

All of these cases involved young toddlers (ages 15 to 39 months), and were detected via their influenza sentinel surveillance system. All three recovered.

 

Today an eagle-eyed Ronan Kelly on FluTrackers has picked up a report from Bangladesh’s IEDCR (Institute of Epidemiology, Disease Control & Research) – dated February 28th – that describes that country’s 4th known H5N1 detection.

 

Unlike the three earlier cases, this one involves an adult male. But as with the others, this patient has fully recovered.

 

 

Fourth H5N1 human case in Bangladesh

A 40 year old male has been diagnosed as fourth case of Human Avian Influenza (H5N1) in Bangladesh. This case has been reported from live bird market surveillance system in Dhaka City on 26 February 2012. This was confirmed by rRT-PCR. The patient is a live bird market worker.

The case presented with cough. Throat and nasal swabs were collected and found positive for H5N1. Presently he is free from symptom. IEDCR & ICDDR,B jointly investigating the case and monitoring the situation. 

In Bangladesh the first case was detected in 2008, second and third cases were found in 2011. 

 

Presumably the IEDCR has notified the World Health Organization, and we’ll get a confirmation in due time.

 

Bangladesh is somewhat unique in that all of their known H5N1 cases have recovered, while apparently experiencing only mild to moderate illness (Myanmar, with only 1 reported case, also has a 100% recovery rate).

 

Contrast this with Indonesia, where more than 80% of the known cases have died, or Egypt, where nearly 40% have succumbed, and it certainly begs the question; why the huge disparity?

 

• Is this just some sort of statistical, reporting, or surveillance fluke?
• Or is the virus circulating in Bangladesh less pathogenic to humans than the one in Indonesia? 
• Or is it perhaps, the people of some regions carry higher levels of community immunity to the H5 virus?

 

Fascinating questions, but for now, answers remain elusive.

Bangladesh: Charges That A Lack Of Compensation Sends Infected Birds To Market

 

 

Photo Credit – FAO

# 6120

 

 

While its not exactly breaking news that some H5N1 infected poultry have made their way into local food markets, most of the countries where the virus is endemic have taken steps to reduce those risks. 

 

Many nations have introduced poultry vaccination against the bird flu virus (albeit, not always a good thing), and most countries have some form of monetary incentive for farmers to cull their flocks if their poultry become infected.

 

Today (h/t Cottontop on the Flu Wiki) we’ve a lengthy and scathing report on the proliferation of the H5N1 virus in Bangladeshi poultry, and deficits in their compensation program that are claimed to be responsible for farmers sending infected birds to market.

 

This via the Financial Express. Follow the link to read it in its entirety.

 

Bird flu affected chickens being supplied to local markets

Arafat Ara Dhaka, Saturday February 4 2012

Bird flu affected chickens are being supplied to the local markets due to lack of monitoring and proper policy support to the poultry farmers by the authority, said sector insiders.

They said the farmers are selling their infected chickens in the markets hiding the information as the government does not compensate the farmers adequately.

(Continue . . . )

While media reports can sometimes slant stories - and part of this story relies on information obtained from unnamed `insiders’ - it is worth noting that the most recent report filed with the OIE on bird flu in Bangladesh ( 15/01/12 Follow-up report No. 37 ) lists 526 outbreaks in that country since 2007.

Map Credit OIE

 

Hardly a reassuring picture that Bangladesh is anywhere close to getting control over their endemic bird flu situation.

Bangladesh: Nipah Claims 5 Lives

 

Nipah/Hendra Virus & Fruit Bat Home Range – WHO

 

# 6098

 

 

Last summer the movie `Contagion’ showed the world how a bat virus might mutate, evolve, and eventually move into the human population. While the movie used a fictionalized MEV-1 virus, it was based on the all-too-real Nipah Virus, which first came to prominence in the 1990s after a deadly outbreak in Malaysia in 1998.

 

While human infections with Nipah (or its Australian cousin Hendra) have been relatively uncommon, when they have occurred they have proven particularly lethal, with fatality rates pushing 60%.

 

During the Malaysian outbreak in 1998, the virus jumped to local swine herds from bats, and along with infecting hundreds of people caused the loss over 100 lives. The virus was then exported via live pigs to Singapore, where 11 more people died.

 

Over the past decade, Nipah has sparked a number of small outbreaks across Southern Asia, although the most intense activity has been centered around Bangladesh.

 

Over the past 48 hours we’ve seen some reports coming out of Bangladesh indicating that several people have been infected with the Nipah virus. Nipah reports out of this region typically come between December and May.

 

Today, the IEDCR issued the following statement, indicating there have been 5 fatalities thus far.

 

Nipah Outbreak at Joypurhat in January 2012

From 20 January 2012, two clusters of Nipah were identified in the Joypurhat Municipality area and Khetlal upazila of Joypurhat district. A joint team of IEDCR and ICDDR,B are working in the field now.

 

Till date (23 rd January 2012), the team identified 3 cases from the municipal area and 2 cases from Khetlal. All 5 cases have died. Laboratory tests for Nipah were done in IEDCR. All four samples collected from suspected cases were positive for Nipah.

 

 

Map Credit- Wikipedia

 

CIDRAP has a nicely done Overview of the Nipah Virus including the clinical symptom chart below:

 

 

Exactly how the Nipah virus is transmitted from human-to-human isn’t well understood, although it is thought to be mostly through direct contact with respiratory secretions or other bodily fluids.

 

For now - while Human-to-human transmission has been documented - only limited outbreaks have been reported.

 

Last February, in Bangladesh: Updating The Nipah Outbreak I wrote about a couple of EID Journal  studies that looked at Nipah transmission between humans.

 

The World Health Organization has this to say about the human-to-human transmission of the Nipah Virus.

 

Transmission

During the initial outbreaks in Malaysia and Singapore, most human infections resulted from direct contact with sick pigs or their contaminated tissues. Transmission is thought to have occurred via respiratory droplets, contact with throat or nasal secretions from the pigs, or contact with the tissue of a sick animal.

 

In the Bangladesh and India outbreaks, consumption of fruits or fruit products (e.g. raw date palm juice) contaminated with urine or saliva from infected fruit bats was the most likely source of infection.

 

During the later outbreaks in Bangladesh and India, Nipah virus spread directly from human-to-human through close contact with people's secretions and excretions. In Siliguri, India, transmission of the virus was also reported within a health-care setting, where 75% of cases occurred among hospital staff or visitors. From 2001 to 2008, around half of reported cases in Bangladesh were due to human-to-human transmission.

Reducing the risk of infection in people

In the absence of a vaccine, the only way to reduce infection in people is by raising awareness of the risk factors and educating people about the measures they can take to reduce exposure to the virus.

 

Public health educational messages should focus on the following.

• Reducing the risk of bat-to-human transmission. Efforts to prevent transmission should first focus on decreasing bat access to date palm sap. Freshly collected date palm juice should also be boiled and fruits should be thoroughly washed and peeled before consumption.
• Reducing the risk of human-to-human transmission. Close physical contact with Nipah virus-infected people should be avoided. Gloves and protective equipment should be worn when taking care of ill people. Regular hand washing should be carried out after caring for or visiting sick people.
• Reducing the risk of animal-to-human transmission. Gloves and other protective clothing should be worn while handling sick animals or their tissues, and during slaughtering and culling procedures.

 

While the Nipah Virus may not pose anywhere near as great of a threat to the world as a pandemic influenza, it does point out the need for increased surveillance and improved public health programs around the world.

Bangladesh To Share H9N2 Bird Flu Virus

 

 

# 5849

 

 

To go along with my blog earlier today (see Dr. Robert Webster’s bird flu concerns), we’ve a report from Bangladesh on an agreement to share samples of the H9N2 bird flu virus with the U.S. CDC for development of a seed vaccine.

 

As has been mentioned here before, H9N2 – while generally producing mild symptoms in humans and poultry – is considered to have pandemic potential.

 

The concern is that it could reassort (swap genes) with other influenza viruses (including H5N1), producing a more virulent and easily transmissible strain.

 

First today’s report from bdnews24.com  (h/t Treyfish on FluTrackers), and then I’ll return with more.

 

 

B'desh to help make bird flu vaccine

Sun, Sep 18th, 2011 9:24 pm BdST

 

Nurul Islam Hasib bdnews24.com Senior Correspondent

Dhaka, Sep 18 (bdnews24.com) – Bangladesh will share a new strain of bird flu virus, identified as a possible pandemic threat, with US Centres for Disease Control and Prevention (US CDC) to develop 'seed virus,' key ingredient to make a vaccine in emergency.

"We will share the vaccine for scientific use," health secretary Muhammad Humayun Kabir told bdnews24.com on Sunday as he confirmed about the sharing of the H9N2 strain of bird flu—A/Bangladesh/0994/2011 (H9N2).

(Continue . . . )

 

 

This article mentions human infections from H9N2 were detected in Bangladesh last March, although no details are provided.  FluTrackers did pick up an FAO/EMPRES report on a human case during that time period which you can read here.

 

Since H9N2 circulates in regions of the world where influenza testing is rarely done, we don’t really know how often this virus infects humans. Over the past dozen years a small handful of cases have been identified – mostly in Hong Kong (see CIDRAP Avian Influenza (Bird Flu): Implications for Human Disease).

 

Adding to the concern, just last week a study was published that looked at level of antibodies to H5N1 and H9N2 flu viruses among rural villagers in Thailand.

 

Evidence for Subclinical Avian Influenza Virus Infections Among Rural Thai Villagers

Clinical Infectious Diseases

Volume53, Issue8

Pp. e107-e116

Benjawan P. Khuntirat1, In-Kyu Yoon1, Patrick J. Blair2, Whitney S. Krueger3,4, Malinee Chittaganpitch5, Shannon D. Putnam2, Krongkaew Supawat5, Robert V. Gibbons1, Sirima Pattamadilok5, Pathom Sawanpanyalert5, Gary L. Heil3,4, John A. Friary3,4, Ana W. Capuano6, and Gregory C. Gray3,4

 

 

In testing 800 villagers they found 38 (4.7%) who were seropositive for the Hong Kong H9N2 flu strain, 45 (5.6%) had antibodies to A/Thailand/676/2005 H5N1, and 28 (3.5%) were shown to be seropositive to A/Thailand/384/2006 H5N1.

 

Interestingly, direct exposure to poultry was not found to be associated with positive serologic findings for any of these avian strains.

 

This study – while limited – suggests that mild (or possibly subclinical) infections by these avian viruses may be occurring in parts of Asia.  

 

Despite causing rare human infection, these avian viruses need to acquire genetic changes before they could spark a pandemic. Which is why we concern ourselves with their ability to reassort with other flu strains.

 

Reassortment (or Shift), happens when two different influenza viruses co-infect the same host and swap genetic material.

 

 

Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).

 

Which means that any two compatible influenza viruses could conceivably – and under the right conditions – generate 256 different combinations by swapping one or more of their 8 (potentially) interchangeable gene segments.

 

 

Last February in PNAS: Reassortment Of H1N1 And H9N2 Avian viruses we saw research from Chinese scientists that created – using reverse genetics – 128 reassorted viruses from the avian H9N2 virus and the (formerly pandemic) H1N1 virus.

 

In mouse testing, they found half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.

 

Research such as this shows the potential for the H9N2 virus to move towards a more `humanized’ pathogen. And with H1N1 and H9N2 both known to be circulating in pigs in Asia, there are ample opportunities for them to co-infect the same host.

 

A few notable H9N2 stories from the past include:

• In December 2008 Revisiting A Malik Peiris Interview On H9N2

• In January of 2010, in H9N2: The Other Bird Flu Threat

• And just this past November Study: The Continuing Evolution Of Avian H9N2

 

Unlike the H7 and H5 avian flu strains, poultry (and swine) infections by the H9N2 virus are not required to be reported to the OIE.  So we have far less data on how widespread H9N2 might be.

 

As we saw in 2009, sometimes a pandemic virus will emerge from an unexpected source, and with a surprising lineage. While the world was waiting for an H5 bird flu to emerge from Asia, we were blindsided by a H1N1 swine flu from North America.

 

All of which highlights the importance of establishing better global surveillance of humans, and farm animals, for the next emerging influenza virus. 

 

Regardless of its strain.

Bangladesh: Conflicting Bird Flu Reports

 

 

# 5564

 

 

We’ve a curious report today in the Financial Express – the only English language financial daily in Bangladesh – on the level of bird flu activity in that country.

 

Since 2007 we’ve often heard of outbreaks of the H5N1 bird flu virus on poultry farms, and the OIE (to whom reporting of H5 & H7 avian flu is mandatory) lists 34 reports totaling 514 outbreaks since May of that year.

 

 

(Photo Credit – OIE Bangladesh H5N1)

The last OIE notification was on May 12th of 2011, which noted 3 recent outbreaks,  and the total number of poultry affected since 2007 is listed as just under 640,000.

 

(Photo Credit – OIE Bangladesh H5N1 Stats)

 

Which makes the following story in the Financial Express - wherein an Industry leader puts the number of outbreaks at 20 times higher – a bit hard to reconcile.

 

A hat tip to Carol@SC on the Flu Wiki for this link.

 

 

Bird flu wreaks havoc in poultry industry: official

 

Dhaka, Friday July 1 2011

Doulot Akter Mala

A third of the country's farm-raised chicken has been decimated by the latest outbreak of the bird-flu, a top poultry farmer has said Thursday, demanding compensation for the affected farms.

 

He told the FE the government needed to roll up its sleeve and help the affected farms with compensation and vaccines in an effort to prevent Avian Influenza from inflicting a mortal blow to the key industry.

 

"We've estimated that 10,000 to 15,000 poultry firms have been affected by bird-flu. Unfortunately the government shows it only 153," said Syed Abu Siddique, president of the Bangladesh Poultry Industries Association,

(Continue . . . )

 

This makes for a sizeable discrepancy between the claims made by the President of the Bangladesh Poultry Industries Association and what has been officially reported to the OIE.

 

The accuracy of either number is difficult to verify, since the OIE can only report what is voluntarily submitted to them.

 

And between this report, and others, there is obviously a good deal of political pressure being exerted in Bangladesh over current and future tax breaks for the poultry Industry, compensation for culled birds, and the importation of vaccine.

 

A cause that would be bolstered by higher poultry losses.

 

There is also the possibility that Siddique is including LPAI outbreaks – such as H9N2 – in his numbers, although only H5N1 is mentioned in the article.

 

We are left with a bit of a mystery it seems.

 

And while I am a bit skeptical that 95% of the outbreaks in Bangladesh are going unreported - that country remains one of the hotspots for bird flu activity in the world - and so it deserves our continued attention.