EID

Andy pointed out a couple of relevant studies in the latest Emerging Infectious Disease journal issue:

Predicting Hotspots for Influenza Virus Reassortment
The influenza pandemics of 1957 and 1968 were deadly; each killed about 1 million people. Both pandemics resulted from the mixing of genetic material of 2 types of closely related flu viruses, called reassortment. This occurs when both viruses infected the same host at the same time. This mixing produced a virus that was more lethal than either alone. This mixing could also happen again. Studies in mice have raised the possibility that mixing of the human seasonal flu virus and the bird flu virus could produce a novel virus that could spread rapidly and kill many people. To determine where such mixing is most likely to occur, researchers evaluated livestock densities and agricultural practices (looking for areas with human and bird flu viruses and high concentrations of pigs). They concluded that the areas at highest risk for a future flu pandemic are coastal and central China and the Nile Delta region of Egypt.

MRSA Infection Risk among HIV-infected Adults
Methicillin-resistant Staphylococcus aureus (MRSA) infections has emerged as an important public health problem. HIV-infected persons are at increased risk for infection and colonization (carrying the bacteria without signs of infection).  Because colonization increases risk for MRSA infection, prevention should be aimed at decreasing colonization. But where and how?  To learn where on the body these bacteria are most likely to colonize, researchers collected samples from HIV-infected patients and monitored these patients over time. Although the nose is consid­ered the primary reservoir of S. aureus, in this study the groin was also frequently colonized with MRSA, and those with groin colonization were more susceptible to developing active MRSA infection later. These data suggest that to prevent active MRSA infections, HIV-infected persons should maintain good general hygiene which includes groin hygiene and take steps to avoid potential MRSA exposures (e.g., by not sharing personal items that may become MRSA contaminated such as towels, bedding, and razors and by keeping cuts and scrapes clean and covered).

Amphibians and bats

I mainly focus on human diseases in this class but over the last week I did branch out a little. Some recently emerging diseases I did not discuss were the chytrid fungus affecting frogs and the fungus that causes white-nose syndrome in bats. Both of these are causing serious conservation problems.

The March 2013 issue of Emerging Infectious Diseases, a publication of the CDC, has a nice review:

Parallels in Amphibian and Bat Declines from Pathogenic Fungi


Abstract
Pathogenic fungi have substantial effects on global biodiversity, and 2 emerging pathogenic species—the chytridiomycete Batrachochytrium dendrobatidis, which causes chytridiomycosis in amphibians, and the ascomycete Geomyces destructans, which causes white-nose syndrome in hibernating bats—are implicated in the widespread decline of their vertebrate hosts. We synthesized current knowledge for chytridiomycosis and white-nose syndrome regarding disease emergence, environmental reservoirs, life history characteristics of the host, and host–pathogen interactions. We found striking similarities between these aspects of chytridiomycosis and white-nose syndrome, and the research that we review and propose should help guide management of future emerging fungal diseases.

Good news everybody!

Browsing through some of the more recent papers on toxoplasmosis I came across this gem from last year:
Toxoplasma gondii Infection in the Brain Inhibits Neuronal Degeneration and Learning and Memory Impairments in a Murine Model of Alzheimer's Disease

Immunosuppression is a characteristic feature of Toxoplasma gondii-infected murine hosts. The present study aimed to determine the effect of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of Alzheimer's disease (AD) in Tg2576 AD mice. 
...
In addition, water maze and Y-maze test results revealed retarded cognitive capacities in uninfected mice as compared with infected mice. These findings demonstrate the favorable effects of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of AD in Tg2576 mice.

So it's not all bad - at least if you're a mouse. A more digesitible summary of this research appeared in the Economist magazine: It's all in your head

Proximity patterns

Here's a neat idea:

To investigate transmission pathways, European researchers of the SocioPatterns collaboration fitted 119 people in a ward of the Bambino Gesù Children's Hospital with radio-frequency identification (RFID) badges. The tags registered face-to-face interactions—and the potential spreading of airborne pathogens.

The original 2011 research paper is here: Close Encounters in a Pediatric Ward: Measuring Face-to-Face Proximity and Mixing Patterns with Wearable Sensors

When Scientific American reported on this research they included a series of striking diagrams that may, or may not, help interpret the results!

Tb hideout

Thanks to Mary for the tip on this report:

Stem Cells: Safe Haven For TB

Mycobacterium tuberculosis (TB) hides out in stem cells deep within bone tissue, where it avoids detection from the immune system and drugs, according to a study published last week (January 30) in Science Translational Medicine.
...
Ninety percent of TB infections are cleared by the body’s immune defenses or by taking anti-TB medication. In the remaining 10 percent of cases, however, TB persists as a dormant, non-replicating infection. Though latent TB infections do not cause symptoms, they can reactivate after years of hiding. An estimated one-third of the global population has latent TB, which accounts for 1.7 million deaths per year—more than any other bacterial pathogen on the planet. 

During the early stages of the disease, active TB bacteria replicate inside human macrophages and dendritic cells. But there is no evidence these cells harbor dormant TB, and the location of the latent reservoir has remained a mystery.

The original paper is in Science Translational medicine this week: CD271+ Bone Marrow Mesenchymal Stem Cells May Provide a Niche for Dormant Mycobacterium tuberculosis.

Chronic Lyme

People will probably interpret this study in a way that fits their favorite theory but on the face of it this paper from a couple of months ago in the New England Journal of Medicine argues against persistent Lyme disease infection being the cause of chronic Lyme disease.

Differentiation of Reinfection from Relapse in Recurrent Lyme Disease
None of the 22 paired consecutive episodes of erythema migrans were associated with the same strain of B. burgdorferi on culture. Our data show that repeat episodes of erythema migrans in appropriately treated patients were due to reinfection and not relapse. 

An editorial in the same issue states the implications quite explicitly:
The issue of relapse versus reinfection has a broader context because of patient-advocacy groups that promote months or years of antibiotic therapy for “chronic Lyme disease.” Moreover, chronic Lyme disease has become a common diagnosis for medically unexplained pain or neurocognitive or fatigue symptoms, even when there is little or no evidence of previous B. burgdorferi infection. Even so, these patients are said to have persistent infection, which can be suppressed only with months or years of antibiotic therapy, and the therapy must be restarted when symptoms recur. As concluded by the Infectious Diseases Society of America, there is no evidence of persistent B. burgdorferi infection in human patients after recommended courses of antibiotic therapy. Although B. burgdorferi infection may persist for years in untreated patients, the weight of evidence is strongly against persistent infection as the explanation for persistent symptoms in antibiotic-treated patients with Lyme disease.

Here's a report on the paper from the New York Times: New Infection, Not Relapse, Brings Back Lyme Symptoms, Study Says

(A) new study finds that repeat symptoms are from new infections, not from relapses.

The results challenge the notion, strongly held by some patients and advocacy groups, that Lyme disease, a bacterial infection, has a tendency to resist the usual antibiotic treatment and turn into a chronic illness that requires months or even years of antibiotic therapy.

New Borrelia on the block

From the LA Times last week:
New Lyme disease-like infection is on the map in U.S.


There a new tick-transmitted spirochete in town, and this wily relative of the organism that causes Lyme disease is probably sickening more than 4,300 Americans a year with relapsing fevers and flu-like symptoms, according to a new report. The good news: A round of common antibiotics appears capable of vanquishing the newly discovered threat.

The organism, called Borrelia miyamotoi, was discovered in 1995 in Japan, but it was not until 2011 that disease hunters found and described evidence that it was making people sick in Central Russia. The organism was found in deer ticks in Connecticut in 2001 and in Northern California in 2006. So it was only a matter of time before the illness it causes was detected in American patients.

That time has come. The New England Journal of Medicine on Thursday published two reports documenting its arrival on U.S. shores. One is a case study of a confused and unsteady elderly woman stricken by Borrelia miyamotoi; the other reports on a broad sampling of blood from patients in New England, where Lyme disease is widespread, and suggests that Borrelia miyamotoi infection "may be prevalent in areas where Lyme disease is endemic in the United States."

The NEJM papers are:
Meningoencephalitis from Borrelia miyamotoi in an Immunocompromised Patient
We report a case of progressive mental deterioration in an older, immunocompromised patient, and even though Koch's postulates were not met, we posit B. miyamotoi as the cause, owing to its direct detection in cerebrospinal fluid (CSF) with the use of microscopy and a polymerase-chain-reaction (PCR) assay.
and
Human Borrelia miyamotoi Infection in the United States
The identification of B. miyamotoi antibody in 18 of our study patients, including seroconversion associated with symptoms in 3 patients, suggests that B. miyamotoi infection may be prevalent in areas where Lyme disease is endemic in the United States.

A cure for Ebola (in monkeys...)

In Science Translational Medicine this week:

Successful Treatment of Ebola Virus–Infected Cynomolgus Macaques with Monoclonal Antibodies

Ebola virus (EBOV) is considered one of the most aggressive infectious agents and is capable of causing death in humans and nonhuman primates (NHPs) within days of exposure. Recent strategies have succeeded in preventing acquisition of infection in NHPs after treatment; however, these strategies are only successful when administered before or minutes after infection. The present work shows that a combination of three neutralizing monoclonal antibodies (mAbs) directed against the Ebola envelope glycoprotein (GP) resulted in complete survival (four of four cynomolgus macaques) with no apparent side effects when three doses were administered 3 days apart beginning at 24 hours after a lethal challenge with EBOV. The same treatment initiated 48 hours after lethal challenge with EBOV resulted in two of four cynomolgus macaques fully recovering.


There's a news report on this paper here: Did Scientists Just Discover a Cure for Ebola?

Xenophobia and disease

An interesting post at the Scientific American blog about the relationship between xenophobia and disease.
Do Wild Bats Hold the Key to Understanding Human Tribal Behavior?

(A) new fungus has arrived in North America, most likely via introduction by humans, and it is killing bats. This fungus (Geomyces destructans) causes “white nose syndrome,” which was first seen in the U.S. in New York in 2006. Where it met the bats, the fungus spread quickly among roosts, killing nearly all of the little brown bats and other bat species in each of the caves in which it appeared. 

But not all is lost. Although it looked as though the little brown bats and several other species might soon face extinction, at least in some regions and perhaps even in North America, the little brown bats have begun to rebound in some places, albeit modestly. A new paper out this week takes notice of one of the reasons they appear to be rebounding, the bats are avoiding each other. Little brown bats (at least historically) tend to roost in large, groups, one next to the other, bumping fuzzies as it were. But not anymore. More and more, this new study, led by Kate Langwig, a graduate student at Boston University, suggests, the bats are spreading themselves out in their roosting caves, their hibernacula. Once, they clumped, warming themselves around the tiny fires of their bodies. Now, they go it alone.

Interestingly, this little brown bat behavior is precisely what the literature on human behavior, xenophobia and tribalism would have predicted. 

Who uses BCG?

The figure shows the countries in orange (USA, Canada and Italy) that never had BCG vaccination campaigns for tuberculosis; countries in purple (much of Europe and Australia) that used to recommend BCG but now do not; and in tan (most of the world) countries that currently have a BCG vaccination program.

This figure is from a PLoS Medicine article in 2011: The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices
which presents data and information about the BCG world atlas. For much more information about this interesting public health issue (to vaccinate or not to vaccinate?) check out their website.

TB in China

A little preview of next week's topic in this week's article, published in the New England Journal of Medicine, on the scale of the tuberculosis problem in China:
National Survey of Drug-Resistant Tuberculosis in China
  
China has a serious epidemic of drug-resistant tuberculosis. MDR tuberculosis is linked to inadequate treatment in both the public health system and the hospital system, especially tuberculosis hospitals; however, primary transmission accounts for most cases. 
The most alarming facts are the extent of drug-resistant strains and a number of news outlets picked up on this story, for example Reuters and the the New York Times.


(O)ne in 10 Chinese patients newly diagnosed or recently treated for TB had a drug-resistant strain of the highly contagious lung disease.
Around 0.5 percent of new cases - equating to 5,000 people a year - were diagnosed with extensively drug-resistant TB, which experts say is almost incurable.

Where did the Haiti cholera outbreak come from?

A Haitian protester in Port-au-Prince last year spray-paints a wall, equating the UN mission in Haiti (abbreviated here as MINISTA) with cholera.

 From the NPR health blog last week reporting on a paper published on June 18 2012 in The Proceedings of the national academy of Sciences (Genomic diversity of 2010 Haitian cholera outbreak strains)

Most researchers currently believe that United Nations peacekeeping soldiers introduced cholera to Haiti in October of 2010.
After all, Haiti hadn't recorded cholera for as long as a century, Nepal had experienced a cholera epidemic in the months preceding the soldiers' arrival, and the Haitian and Nepalese cholera strains were found to be nearly identical.
But it's not that simple, says a research group based at the University of Maryland.
  These researchers have found two very different cholera strains in some of the first Haitians to be struck by the disease.

To publish or not?

Some of you may have read about an interesting disease related debate that is going on right now and is attracting quite a lot of media attention. It concerns the H5N1 strain of influenza that appears to have a high mortality rate in people but is currently poorly transmitted between people (if it is even transmitted at all).

In 2011 two teams of scientists created mutant strains of H5N1 influenza (ie avian or bird flu) that could be more easily passed between mammals in a laboratory setting (ferrets are the animals of choice for flu studies apparently). Scientifically this is interesting research and could address several public health issues: can this strain become more easily transmitted without losing its virulence? Which changes should we watch out for? How many mutations does such a change require?

However as the papers were reviewed the US National Science Advisory Board for Biosecurity (NSABB) recommended that the results of the two studies should only be published in a redacted form. They advised that methods and details should be left out for fear the research could fall into the wrong hands and be used to create a pandemic that might kill tens of millions of people. This unprecedented move sparked a broader debate about censorship and responsibility in potentially dangerous research.

It also provoked some sensational headlines:
Controversial 'Armageddon' super virus recipe to stay secret - for now - Sydney Morning Herald

In a meeting last month the World Health organization came to a different conclusion. A panel of 22 experts  concluded that the mutant flu studies should be published in full. They argued that redaction would likely be ineffective and that the benefits outweighed the potential risks.

Nature have put together a web special on the H5N1 controversy that compiles a variety of papers, reports and commentary (and is also the source for this fantastic chicken image).

Malaria proof mosquitoes

A 'malaria proof' mosquito' would be an valuable tool in the fight against malaria. It looks like scientists have created just such a mosquito - through a combination of disrupting the parasite development and reducing the mosquitoes lifesapn (as we discussed in class). Now all we need is a way to give such mosquitoes a competitive edge so that they replace the
 native mosquitoes...

Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes. PLoS Pathogens, 2010;

It was known that the Akt enzyme is involved in the mosquito's growth rate and immune response, among other things," Riehle said. "So we went ahead with this genetic construct to see if we can ramp up Akt function and help the insects' immune system fight off the malaria parasite."
The second rationale behind this approach was to use Akt signaling to stunt the mosquitoes' growth and cut down on its lifespan.
"In the wild, a mosquito lives for an average of two weeks," Riehle explained. "Only the oldest mosquitoes are able to transmit the parasite. If we can reduce the lifespan of the mosquitoes, we can reduce the number of infections."

Toxoplasmosis, suicide and brain cancer

In addition to the effects I mentioned in class Toxoplamsosis has also been linked to increased rates of suicide: Toxoplasma gondii Seropositivity and Suicide Rates in Women
In conclusion, the results suggest that a positive relationship between rates of infection with T. gondii and suicide is apparent in women of postmenopausal age. Prospective studies are necessary to further confirm this association predictively and to explore mechanisms mediating this relationship.

and brain cancer -
Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common.
Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

Both these papers are from 2011. It's pretty clear there's something going on even if we don't know exactly what it is.

Draft genome

Here is the latest paper on bubonic plague and the Black Death, from just a few months ago:
A draft genome of Yersinia pestis from victims of the Black Death
Although the study confirmed the basic story from last year - that the bacteria that caused the Black Death was the ancestor of all modern bubonic plague strains - it did not find any obvious change in virulence genes that might account for the huge mortality that the Black Death caused.

'(W)e posit that molecular changes in pathogens are but one component of a constellation of factors contributing to changing infectious disease prevalence and severity, where genetics of the host population, climate, vector dynamics, social conditions and synergistic interactions with concurrent diseases should be foremost in discussions of population susceptibility to infectious disease and host–pathogen relationships with reference to Y. pestis infections.'

Tick removal

Many people seem to have heard of one or other supposed foolproof way to remove ticks. None of them seem to work very well though, or be any better than simply pulling the tick out. At least not according to 'Evaluation of five popular methods for tick removal' by Glen Needham from the Acarology laboratory at Ohio State.

It is recommended that the tick be grasped as close to the skin as possible with curved forceps; if these are not available, use tweezers or protected fingers. Pull straight up with steady even pressure. If cement or mouthparts remain, then extract if that is practical. Disinfect bite site before and after tick removal.

Commercial tools that function in this manner may make the task slightly easier.

Here's a video guide to removing ticks from the University of Rhode Island's TickEncounter Resource Center.

Good news for tea and coffee drinkers

It's amazing how many times there is a story in the news at the same time we cover the topic in class.

In the news at the moment is the interesting story that coffee and tea drinkers could be at lower risk of a developing a deadly drug-resistant staph infection.

As part of the 2003-04 National Health and Nutrition Examination Survey (NHANES), more than 5,000 Americans from across the country were tested for methicillin-resistant Staphylococcus aureus — better known by its abbreviation, MRSA — in the nasal cavity. Although carrying MRSA in the nose is not at all dangerous by itself, some studies show that nasal colonization may put people at higher risk of systemic MRSA infection throughout the body, and that can be fatal.


The results of the NHANES testing, published in the July/August issue of the journal Annals of Family Medicine, showed that 1.4% of the nationally representative survey participants had nasal MRSA carriage. However, people who drank coffee or hot tea at least once a month were only about half as likely to be infected as those who did not — even after adjusting for age, race, sex, recent antibiotic use and hospitalization history, and a few other variables.

Coffee and tea drinkers saw advantages of about the same magnitude, no matter which drink they favored. The study authors say they cannot be sure why people drinking tea or coffee might be less likely to have nasal MRSA carriage, but that it could be the result of antimicrobial compounds known to exist in the beverages.

The actual research paper in the Annals of Family Medicine, Tea and Coffee Consumption and MRSA Nasal Carriage, is very readable. It's also interesting to see that statistic that 1.4% of people had nasal MRSA. Given that about 25% of people are carriers of S.aureus (actually 28% in this study) it means that about 1 in 17 of those carriers had the MRSA strain.

Thermal scanning for flu

If there is an influenza pandemic then initial attempts at isolating the outbreak, or prevent its entry into particular countries, may involve the use of infrared thermal image scanners (ITIS) at airports to detect people with elevated body temperatures characteristic of influenza. We saw this in the 2009 H1N1 (Swine Flu) pandemic. Analysis suggests that countries that adopted the policy managed to delay disease entry for 7-12 days compared to countries that did not: Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1). Of course there may be other differences between these two types of countries. Correlation is not causation...

A paper in PLoS ONE in January this year, Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study, looked at a sample of 1275 airline passengers who agreed to be screened, have their temperature actually measured and give a respiratory sample. Six of the travellers had a fever and thirty of the travellers tested positive for influenza. But none of the influenza-positive travellers had a temperature high enough to be considered in the fever group!

Our findings therefore suggest that ITIS is unlikely to be effective for entry screening of travellers to detect influenza infection with the intention of preventing entry of the virus into a country.

I'm sure we'll see more of these thermal scanners in airports in future pandemics even if they are fairly useless. Why? Because it makes it look like somebody is doing something (even if it is useless). Just like the rest of airport security

Flu trends

Google has been tracking flu trends for some time by analyzing people's choice of search terms. This method has been very successful and they can usually pick up trends a few weeks before the CDC data. In 2009 a variety of workers from Google and one from the CDC published a paper in Nature describing their technique: Detecting influenza epidemics using search engine query data.

For epidemiologists, this is an exciting development, because early detection of a disease outbreak can reduce the number of people affected. If a new strain of influenza virus emerges under certain conditions, a pandemic could ensue with the potential to cause millions of deaths (as happened, for example, in 1918). Our up-to-date influenza estimates may enable public health officials and health professionals to better respond to seasonal epidemics and pandemics. 
 
The graph above shows, for the United States as a whole, that the peak flu season is usually in February and that we are probably past the peak this year. You can also see how unusual last year was, pandemic years are always different. The big peak in October is from 2009-2010. The same pattern was seen in California except that our peak flu season seems a bit less predictable.