The influence of weather on infectious diseases has been recognized for centuries. In our own experience, we know that some diseases like influenza are more common in the winter or others thrive better in the tropics. The effects of climate – weather over long periods of time - on infectious diseases have been getting a lot of attention lately. I was recently interviewed for a Focus Earth episode on infectious diseases and climate change. The introductory clip frames a debate between a calculated scientific position for the impact on individual infectious disease versus broad generalizations about global warming. It makes for great television and offers an opportunity to educate and engage the public about the health impact of climate change. In this case, both positions are true but highlight the difficulties in communicating the complexity of health effects from climate change – especially when we try to isolate the effects of climate from other biologic, ecologic, or social changes that lead to changes in infectious diseases.

There is no doubt that a dramatic increase in global temperature will cumulatively have a profound negative effect on health. This impact will be from a combination of factors including direct heat effects, increase in rainfall, extreme weather events including droughts and floods, and changes in air quality. There will also be changes in climate-sensitive infectious diseases such as zoonotic, vector-borne, environmental (fungi), and food/water borne diseases. These effects are most likely to be felt in tropical and semi-tropical countries which are least likely to be able to adapt to the changing climate. However, specific predictions about individual infectious diseases requires both 1) more information on the impact of climate and the geographical distribution of existing diseases, reservoirs, vectors, and pathogens which are all interconnected (for more information about infectious diseases at the interface of people, animals, and the environment, check out: www.cdc.gov/nczved/framework/); and 2) the ability of individual communities to adapt to these changes.

The need for better information to drive prediction and preparedness activities cannot wait. The effects of recent climate change are already evident in the northward presence of Vibrio vulnificus infecting oysters in Prince William Sound, the tropical Cryptococcus gattii fungal infections in the Pacific Northwest, expansion of tick-borne encephalitis in Sweden, and suggestions of shorter respiratory syncytial virus seasons in the United Kingdom. For more on CDC’s climate change activities visit Climate Change and Public Health. Please also share your thoughts.

These are the tools used in multiple-locus variable-number tandem-repeats analysis (MLVA), a technique that has the potential to identify subtle differences at the genetic level between closely related bacterial strains.

When CDC is working on an outbreak of foodborne illness, it’s our goal to pinpoint the source as quickly and precisely as possible so we can prevent any further threat to public health. For several years now, the PulseNet Methods Development and Reference Unit (PMDRU) has been developing and validating new methods to complement pulsed-field gel electrophoresis (PFGE), which is currently the standard typing method used in outbreak detection. The method that we have found most helpful in detecting subtle differences between closely related bacterial strains is a technique known as multiple-locus variable-number tandem repeat analysis (MLVA).

Since MLVA is still a fairly new technique, most state health laboratories don’t yet have the capability to perform it themselves. They have to send their samples to CDC for testing. As a microbiologist in the PMDRU, my job is to perform the hands-on testing on the E. coli and Salmonella strains we receive from the states.

The recent outbreak of E. coli 0157:H7 related to eating raw cookie dough is a great example of how we’ve put this new technique to work. A week after our PulseNet colleagues identified the potential cluster of illness, we requested samples from around the country that fit the PFGE pattern we were investigating. Within two weeks it was clear that most of the state samples shared the same MLVA pattern as well.

Over the next few weeks, samples continued to come in and MLVA was run as soon as they arrived. Meanwhile, the epidemiologists at the local state health departments and CDC were busy conducting interviews on the case patients. Interestingly, a very unusual vehicle, raw cookie dough, emerged as a likely source for this outbreak.

This image, called an electropherogram, is a snapshot of different fragment sizes (green, blue and black peaks) of genomic DNA from an E. coli O157:H7 isolate. Finding another isolate that gave the same peaks would tell scientists that the isolates were closely related and could possibly be part of the same outbreak. Armed with this kind of information, scientists can refine their search to find what's making people sick.

On June 29, the Food and Drug Administration (FDA) notified us that they had been able to isolate E. coli O157:H7 from cookie dough and the request was made to send the strain to the CDC for immediate testing. We tested the isolate immediately upon arrival, only to discover that the MLVA pattern was quite different from the main outbreak pattern.

Even though we haven’t found our “smoking dough” yet, the information gathered by interviewing patients strongly supports the cookie dough theory. Unlike other older DNA fingerprinting techniques, MLVA helped us see more accurately which patients shared a common source for their illness.

Related Links

More information about PulseNet and its role in foodborne outbreak detection can be found at http://www.cdc.gov/pulsenet/.

The possibility that E. coli O157:H7 was a contaminant in cookie dough surprised even the most experienced microbiologists here in CDC’s Enteric Diseases Laboratory Branch. E. coli O157 is a common culprit of a severe diarrheal illness, usually caused by eating contaminated and undercooked ground beef or drinking unpasteurized apple juice. It shouldn’t have even been on the “Who’s Who” list of the top bacterial contaminants.

We are Gerry Gómez and Mike Humphrys, two microbiologists in the Enteric Diseases Laboratory Branch. We identify disease-causing bacteria from foods and from specimens taken from sick people.

As microbiologists we have to be flexible and creative in our approaches to isolate bacteria from all different kinds of foods. Our usual method is to mix the food with enrichment broth and see what grows after 18 hours of incubation. For this investigation, we made cookie dough slurry. Then we added tiny magnetic beads treated so they’ll stick to the antigen on the cell wall of E. coli bacteria. If present, E. coli cells would stick to the beads, and then we used a magnet to pull the beads (and any bacteria) out of the slurry. Now we had a better chance of isolating E. coli from the cookie dough.

An important part of our investigational process is collecting and sharing data from laboratories across the U.S. For the cookie dough outbreak, 13 laboratories tested 164 various cookie dough products.

E. coli growing on blood agar.

We found that the chocolate chip cookie dough that sick people had eaten didn’t come from only one batch.

We in EDLB never know what food products will come our way, but we’re willing to test just about anything to confirm a hypothesis. Even experienced microbiologists who have “seen it all” can be surprised and challenged by an old bacteria turning up in a new place.

“Wildlife Health from Land to Sea: Impacts of a Changing World.” That was the theme of the 58th annual meeting of the Wildlife Disease Association, held earlier this month. I had the pleasure of attending this conference along with several colleagues from the National Center for Zoonotic, Vector-borne, and Enteric Diseases (NCZVED).

Our work in NCZVED focuses on understanding infectious diseases in an interconnected world of people, animals and environment. Attending, and this year sponsoring, meetings like this one help us stay in touch with the scientific community that looks at the health and diseases of wild animals.

Jim Mills of NCZVED’s Special Pathogens Branch is now the editor of the association’s Journal of Wildlife Diseases and it was his idea to have a stronger presence at the annual meeting this year. Tracee Treadwell, NCZVED’s Associate Director for Zoonotic and Epidemiologic Science, was a plenary speaker, emphasizing the importance of wildlife professionals thinking about how their science can be applied to human health. And Charles Rupprecht of CDC’s rabies program presented on the role of bats in lyssavirus, the group of viruses that includes rabies.

Karoun Bagamian presents her field studies on hantavirus transmission.

With a full week of workshops, presentations and field trips, the conference offered an opportunity to meet the members. Public health is one of ten areas of focus for the association, and we found there were many papers and posters presented on diseases that affect both people and animals. Hantavirus, Ebola hemorrhagic fever and Rift Valley fever were all discussed, and the science, whether you’re looking at animals or people, is similar and complementary. Understanding animal diseases and the environment gives us keys to understanding disease in humans. CDC has much to contribute to, and gain from, discussions in the years ahead.

In addition to being a part of the presentations, we created a poster describing the mission of NCZVED and even found a way to incorporate a space where we could show video of CDC staff working in a variety of settings. We found that was a great way to engage the meeting attendees.

Jim Mills of CDC's Special Pathogens Branch and conference attendees enjoy a moment discussing CDC's work in animal and human health.

We made a lot of new friends at the conference. One of the Wildlife Disease Association members is studying the transmission of Ebola hemorrhagic fever in non-human primates in Africa, and he’s coming to visit us so we can talk about possible collaboration.

Opportunities like this to learn from each other and work in partnership are one of the keys to our future success in dealing with infectious diseases.

The Public Health Matters blog welcomes requests from its readers. Recently, a reader asked us to address the issue of Hepatitis B in Kuwait. Dr. Frank Mahoney, a CDC medical epidemiologist who has worked extensively in the Middle East, wrote this response:

The global burden of disease due to cirrhosis (hardening) of the liver and hepatocellular carcinoma (HCC—liver cancer) is high (~ 2% of all deaths) and expected to increase over the next 20 years. Liver cancer is already the 4th leading cause of cancer deaths worldwide. Studies of patients with cirrhosis and HCC in the Eastern Mediterranean Region indicate more than 75% is caused by hepatitis B virus (Hep B) or hepatitis C virus (Hep C) infection. The World Health Organization (WHO) estimates approximately 4.3 million persons are infected each year with Hep B and 800,000 persons with HCV in the Eastern Mediterranean Region. Numerous studies suggest that most Hep B and Hep C infections in the Eastern Mediterranean Region are acquired due to unsafe injections and medical procedures. The cost to treat patients with chronic Hep B or Hep C infection far outweighs the cost of implementing prevention programs (like immunizations and infection control). A wide-ranging strategy is urgently needed to prevent spread of these blood-borne pathogens throughout the Eastern Mediterranean Region and other parts of the world.

Kuwait is a small country within the Eastern Mediterranean Region, located between Iraq and Saudi Arabia and bordered on one side by the Persian Gulf. In 1990, Kuwait was one of the first countries in the Eastern Mediterranean Region to introduce Hep B vaccine in their national immunization program. Before vaccine introduction, ~ 25% of adults had evidence of Hep B infection, including 2.5% with chronic (lifelong) infection. Hep B vaccination began with infant immunizations and included the delivery of a dose at birth to prevent Hep B transmission from mother to child. Kuwait reports high numbers of children receiving the Hep B vaccine. While no formal studies have been conducted to document the impact of introducing Hep B vaccine in Kuwait, it is likely that the program has significantly protected children born since 1990, resulting in a reduced prevalence of chronic Hep B infection and associated morbidity and mortality (chronic liver disease and HCC). Kuwait also offers Hep B vaccination to health care workers with occupational exposure to blood.

WHO estimates about 1.8% of the Kuwait population have evidence of Hep C infection. The epidemiology of Hep C infection in Kuwait is not well-studied.

Read “Isolation of genetically diverse Marburg viruses from Egyptian fruit bats” from the July 2009 issue of PLoS Pathogens.

APHL/EID Fellow Amanda Candee collecting environmental samples from a sheep pen in western Colorado. Sheep are a major reservoir for Coxiella burnetii.

Q fever is a disease caused by the bacterium Coxiella burnetii, which can be transmitted to humans from animals such as sheep, goats, and cattle. C. burnetii is considered a possible bioterrorism agent because it is quite hardy in the environment, infects people who breathe aerosols containing the organism, and has a very low infectious dose (one organism can cause disease in a susceptible person).

Recently, we at CDC’s Rickettsial Zoonoses Branch and our colleagues at the National Center for Health Statistics tested blood samples from the 2003-04 National Health and Nutrition Examination Survey (NHANES) and found that 3.1% of the general U.S. population have antibodies to C. burnetii. This means that as many as 9 million people in the U.S. have been exposed to Q fever at some point in their lives!

Additionally, in collaboration with the Rollins School of Public Health at Emory University, we tested 508 veterinarians and found that slightly more than 22% had antibodies to C. burnetii. This suggests that a large proportion of veterinarians become infected with these bacteria, probably through exposure to infected livestock. An increasing number of Q fever cases have also been reported in military personnel serving in Iraq and Afghanistan. Lastly, we at RZB conducted a study to detect C. burnetii DNA in environmental samples collected across the U.S. (6 states including west coast, southwest, upper Midwest, east coast, southeast) and found 23.8% of all samples positive!

APHL/EID Fellow Teresa Wolfe and James Glover (California State Health Department) collecting environmental samples at a grocery store in northen California to test for C. burnetii.

So why are these findings so surprising? Fewer than 200 cases of Q fever are reported each year in the United States, meaning that most cases of Q fever are going unnoticed.

The good news: Most people infected with C. burnetii show no signs of disease or develop a mild illness, and the vast majority of infected people recover from Q fever, even without treatment.

The bad news: About 1% of infections may become chronic and lead to life-threatening inflammation of the heart. Chronic infection is more likely in people who have pre-existing heart problems or weak immune systems. Pregnant women are also at high risk of infection that can lead to complications for the mother and fetus.

Now that we know Q fever is seriously underreported, we are working on new ways to prevent transmission to humans and diagnose cases early.  By identifying cases early, we can prevent some of the complications caused by this disease.

For More Information

• C. burnetii Antibodies in US Veterinarians
• Q Fever and the US Military

Egyptian fruit bats at home in the Python Cave, Maramagambo Forest, Queen Elizabeth National Park, Uganda.

Marburg hemorrhagic fever is one of the world’s deadliest diseases. While not always fatal, infection with the Marburg virus generally causes serious illness. There is no vaccine or drug therapy available for those who become infected and we know that as many of 90 percent of those infected during outbreaks have died.

Members of CDC’s Special Pathogens Branch recently were part of a team of scientists that successfully isolated the Marburg virus from a common species of African fruit bat, Rousettus aegyptiacus. Scientists have been looking for the Marburg virus since the first recognized outbreak in 1967, but have never been able to definitively identify the natural host.

The team traveled to Uganda in August 2007 and May 2008 to conduct a study in the Kitaka mine near Ibanda village in western Uganda. The mine was the site of a small 2007 outbreak of Marburg hemorrhagic fever among the lead and gold miners who work in it.

The team suspected bats might be a reservoir for the virus. By testing tissue samples from apparently healthy bats they were able to capture at that site, they were able to isolate actual infectious viruses, and genetically link them to the virus that infected those miners. That link suggests the bats were the source of the 2007 outbreak.

The large populations of African fruit bats in these mines, as well as in the caves that are popular tourist attractions in Africa, offer many opportunities for close contact between bats and humans. By identifying the natural source of this virus, appropriate public health resources can be directed to prevent future outbreaks.

The team had hoped to find the natural host of the virus when they started their work in the Kitaka mine. There’s more work to do as the team continues to study transmission of the Marburg virus in nature with their colleagues from the Uganda Wildlife Authority and the Uganda Virus Research Institute.

Read “Isolation of genetically diverse Marburg viruses from Egyptian fruit bats” from the July 2009 issue of PLoS Pathogens.

Members of CDC's Special Pathogens Branch standing near harp trap preparing to capture fruit bats in the Python Cave in Uganda.

The road to last month’s cookie dough recall started when CDC scientists reviewed information collected through PulseNet, a national network of laboratories that perform DNA “fingerprinting” of foodborne bacteria like E. coli O157:H7, Salmonella, and Listeria. These fingerprints are plugged into a database that CDC and its state partners routinely scan. I’m a PulseNet database manager at CDC and one of my jobs is to identify “clusters” - groups of illnesses that share the same fingerprint.

On May 14, 2009, I performed a routine weekly cluster search of the E. coli national database and found one of our “common” patterns rearing its head as it does each week. There’s lots of E. coli out there and some strains are more common than others. In these cases, we have to make an educated guess with each review – is there something different about this common occurrence that might signal an outbreak? In other words, “Ignore this or report it?”

In this case, we were seeing an increase in cases. It wasn’t extremely high, but for May it was higher than usual. At the same time, we got an e-mail notification from our state lab colleague in Massachusetts stating they had patterns that matched the potential cluster. At this point, I decided to report it.

PFGE gel produced with outbreak strain in lane 7

Once our epidemiologists started looking into this cluster our work really began. The PulseNet database team started receiving requests for updated case counts with demographics and pattern frequency graphs. Our lab was asked to perform additional tests to fine tune the distinction between cases, due to the common nature of this pattern.

Little did we know that this common pattern cluster of E. coli O157:H7 would turn into one of the more challenging outbreaks so far this year! Soon after the investigation began, it appeared that raw cookie dough may be the source of the cluster, something that still puzzles the experts!

PulseNet is a cluster detection system that helps us know quickly if something is not right with our food supply out in the public. Improvements to surveillance can always be made, and one thing that would be great to improve is how to more easily identify true clusters of our common patterns as many of these may be outbreaks that go unnoticed. Next generation methods are in development and it is going to be interesting to see what the future has in store for PulseNet, surveillance, and cluster detection!

Workshop participants developed several alternative designs before agreeing a layout.

I work in CDC’s Special Pathogens Branch (SPB) where we study highly infectious viruses. My job is health communications and I’ve just returned from Uganda. I was there to work with the Ministry of Health and health educators from Uganda’s Western Districts to create materials that would help keep people there safe from Ebola and Marburg hemorrhagic fevers. Unfortunately, Uganda has seen more than its share of these diseases since the first cases were diagnosed in 1967.

Ebola and Marburg hemorrhagic fevers are rare and deadly diseases with no vaccine or cure. We’re not really sure how they’re passed from their animal hosts to humans, but we know that once someone gets Ebola or Marburg, it can pass from person-to-person by direct contact. Explaining the best ways to stay safe from exposure and how to stay healthy if the disease is present in their community is critical to preventing and controlling outbreaks.

For these particular diseases, we know that many outbreaks start in remote health care settings or happen when family and community members prepare a body for burial. We must get out the important messages of segregating these patients from others and using strict precautions for personal protection if you’re going to be in contact with someone with Ebola or Marburg.

In our meeting, my Ugandan colleagues and I spent three days developing messages and — most importantly — getting the view from the district level of what would work. We agreed to develop a series of six printed products targeted to different audiences. I’ll be spending the next few months developing brochures and posters, and following up with everyone to see how the materials are received.

It takes being on the ground where things are happening to understand what people need. My Ugandan colleagues made me very welcome and it was exciting for us all to combine our efforts to keep people healthy.

The workshop participants (clockwise around the table): Mrs. Sharminah Kauma from the Ministry of Health/Kampala; Mr. Gabriel Tibuhwa, Kasese District Health Educator; Mr. Vincent Mugisha, DHE Ibanda District; Mr. Charles Babikunyamu, DHE Bushenyi District; Mr. Paul Kagwa, Asst. Commissioner Health Services, Health Promotion and Education, Ministry of Health/Kampala; Mr. Maari Karungi, DHE Kanungu District; Mr. James Ndezika, Bundibugyo District Health Educator, Mr. Samuel Kahirita, DHE Kamwenge District.

In the U.S., human rabies is rare, thanks mostly to the availability of rabies vaccination and the elimination of dog rabies. But in many other countries around the world, dog rabies is very common and people are at greater risk. When a person travels or immigrates from an area of higher risk (like Mexico) to an area of lower risk (like the United States), they may encounter obstacles in getting diagnosed correctly if they have rabies. A recent human rabies case from California demonstrates the challenges that can arise when attempting to administer care to a person from another country.

The patient returned to the home of an aunt. The next day, he collapsed, and when paramedics arrived, the patient was not breathing, unresponsive, and could not be resuscitated. After the boy’s death, the ED physician began to consider rabies as the cause of his illness for two primary reasons: he presented several rabies symptoms (hydrophobia, aggressive behavior, and depression) and came from a region of Mexico where dog rabies is very common. An investigation was initiated to confirm the physician’s suspicion. After interviewing family members, talking with Mexican health authorities, and conducting lab tests, much was learned:

• There were several stories about how he was exposed to rabies — one that implicated a dog bite and another a fox bite the patient had received approximately 3-4 months prior to leaving Mexico.
• The rabies virus variant responsible for the patient’s infection was characterized as a bat rabies virus variant which had not been previously identified in the U.S. or in Mexico.
• This case represented the first case of imported rabies in the United States not attributable to a dog rabies virus variant

What might this mean for rabies prevention and control between lower and higher risk countries? Well, a few things pop to mind as being critically important:

• Sharing information between countries about persons affected as well as variants of the virus can be helpful in identifying new variants of a disease and implementing control measures and prevention education in both countries
• Establishing collaborative efforts, especially along border regions, among entities that have a stake in human and animal health is key too. Having procedures for sharing cases of disease among people and animals can lead to faster identification of cases and outbreaks as well as to prevention and control measures.

For more information, please see the MMWR article from July 10, 2009

• Imported Human Rabies - California, 2008