Sunday, December 30, 2012

New Study Explores Relationship Between Biodiversity, Vector-borne Diseases and Economics

Aedes aegypti mosquito (one
of the mosquitoes that carries
the dengue virus; cdc.gov)
Here is an interesting article by Bonds and colleagues in PLOS Biology. Via creative statistical modeling techniques, these authors examined the relationship between the 'latitudinal gradient in income' (the fact that there are more poor people living in the tropics) and vector-borne and parasitic diseases (diseases like malaria that are carried by mosquitoes).

The authors found that vector-borne diseases (VBDs) have significantly affected economic development, and that VBDs are affected by underlying ecologic conditions, especially biodiversity. Interestingly, their model predicts that the burden of VBDs will rise (and local economies will suffer) if biodiversity falls.

Dengue risk map (for past 3 months); tropical areas are
disproportionately affected by many tropical infections;
www.healthmap.org/dengue/index.php
An example of a VBD is dengue, a viral disease carried by mosquitoes (the disease 'vectors'). Both the dengue virus and its mosquito vectors are influenced by local ecosystems. One example of how influencing an ecosystem can affect a VBD is the release of genetically altered mosquitoes into an area to help control the spread of dengue disease. This practice has been used in multiple locations to control dengue spread via limiting the local mosquito population's ability to reproduce.

An example of a VBD that has potentially emerged due to relatively poor biodiversity is Lyme disease; this is a bacterial infection carried by ticks; there were over 24,000 cases in the US in 2011.

The authors note that diverse, well-functioning ecosystems may have a positive effect on the health of a given population via decreasing the burden of vector-borne diseases. This, in turn, will positively affect a given area's economy. This research is intriguing and more research into the relationship between the burden of VBDs and ecology is warranted.

Friday, December 28, 2012

Importance of "Super-spreaders" in Infectious Disease Outbreaks

Entering Honduras during the H1N1 influenza
pandemic, June 2009
Here is an interesting article from Slate looking at the role of "super-spreaders" in infectious disease outbreaks. This refers to a sub-population of individuals who are more likely to spread an infectious disease than others; it is believed such "super-spreaders" played a role in the SARS pandemic. Identifying these individuals may have a role in managing global infectious disease outbreaks.

At the hospital level, Polgreen and colleagues have studied this phenomenon as it applies to hand hygiene and disease spread. Their work supports the idea that certain healthcare workers are more likely to spread an infectious disease, and has implications for targeting these individuals to prevent disease spread (via such things as optimizing hand hygiene, et cetera).  

Wednesday, December 26, 2012

Time To Stop Smoking: New Study Shows Deadly Effect of Smoking on People with HIV

Here is a study by Helleberg and colleagues looking at smoking-related mortality in HIV patients in Denmark. For people with HIV (in a country where HIV care is organized and antiretroviral therapy is free), smoking was associated with more years of life lost than HIV itself.

These authors looked at 2,921 people with HIV followed in the Danish HIV Cohort Study (from 1995-2010) with 10,642 controls taken from another large population-based cohort.

HIV positive smokers were 5.3 times more likely to die from a non-AIDS related death (cardiovascular disease, cancer, et cetera) than HIV positive non-smokers. AIDS related mortality was higher in HIV positive smokers, as well; they were 4 times more likely to die from an AIDS-related death than HIV positive non-smokers.

The authors estimate that a 35 year old HIV positive smoker has a life expectancy of approximately 63 years; an HIV positive non-smoker has a life expectancy of 78 years. In terms of years of life lost, smoking was associated with 12.3 years of life lost (versus only 5.1 years lost associated with HIV).

Although one could argue that these findings may be difficult to extrapolate to settings outside Denmark (where, again, HIV care is well organized and antiretrovirals are free), these findings are compelling and have implications for managing HIV positive patients worldwide. Although healthcare providers are well aware that smoking causes all sorts of health problems and is associated with increased mortality, this study quantifies the deadly effect of smoking on people living with HIV.

In an era where antiretrovirals have transformed HIV into a chronic illness, we need to re-double our efforts in counseling/ supporting HIV positive patients to stop smoking.

Tuesday, December 25, 2012

An Update on Antibiotic Stewardship: From the 22nd European Congress of Clinical Microbiology and Infectious Diseases

Here is a nice article by Canton and Bryan that provides an update on Antibiotic Stewardship as reported at the 22nd European Congress of Clinical Microbiology and Infectious Diseases. The article references several poster presentations from this meeting as well as multiple studies that are already in print.

Infection with antibiotic-resistant organisms
has been associated with an increased
risk of death (cdc.gov)
Antibiotic Stewardship is a field of study and practice focused on decreasing the emergence of antibiotic resistance and optimizing antibiotic use.

A survey project that polled 324 facilities from six continents revealed that over half of these have Antibiotic Stewardship Programs (ASPs), although only 1/3rd had formally assessed these programs' impact. Those programs that had done formal assessments found that stewardship efforts were associated with decreased use of broad-spectrum antibiotics and decreased costs. 

cdc.gov
Targeted interventions in long-term care facilities (a known reservoir of antibiotic resistant organisms) led to decreased antibiotic use in these settings. 

Some countries are better stewards of antibiotics (in the outpatient
setting) than others. Antibiotics are often prescribed for viral
upper respiratory illnesses, a practice that drives antibiotic
resistance and has no affect on these infections (antibiotics are active
against bacteria, not viruses) (cdc.gov)
A study by Denes and colleagues found that there was poor adherence by primary care doctors to guidelines for UTIs in France. 

There are a paucity of new antibiotics in the "pipeline." This is especially true for multi-drug resistant (MRD) gram-negative infections. 

The article (part of a two-part series) by Canton and Bryan is a nice overview of the research presented at the European Congress of Clinical Microbiology and Infectious Diseases. These studies add to the growing Antibiotic Stewardship literature. However, critical questions still remain.  What interventions are best for decreasing the emergence of antibiotic resistance? What interventions are best in certain settings (hospitals/ long-term care facilities/ the general practitioner's office)? We know ASPs can lead to decreased use of broad-spectrum antibiotics and reduce costs, but what really works in terms of decreasing resistance? Robust, high-quality research is needed to answer these critical questions. 

The antibiotic pipeline is "drying up." This is especially
true for drugs to combat resistant gram-negative
infections (cdc.gov)
Beyond this, the future is still bleak in terms of new antibiotics to combat multi-drug resistant gram-negative infections. It is critical we preserve the antibiotics we have and reduce the spread of resistant organisms. 

Monday, December 24, 2012

Global Health Outlook: Living Longer, But Sicker: More Commentary on the Global Burden of Disease Study

Source: NASA
Here is a nice opinion piece from The New York Times about the recently released Global Burden of Disease study; see here for my initial comments on this ambitious project.

The Global Burden of Disease study, again, was a herculean effort. This work involved nearly 500 researchers and describes in exquisite detail current global morbidity and mortality, drawing contrasts to similar data from 1990.

In broad strokes, fewer children under five years of age are dying and people are living longer, but with chronic diseases (such as diabetes and osteoarthritis). Diseases that were once primarily associated with developed nations (such as heart disease and cancer) are now much more frequent causes of death in the developing world.

La Hicaca, Honduras (one of our principle clinic sites)
I work with a group of volunteer physicians and other health professionals in the Yoro area of northern Honduras. One of the things we noted when we began working in this area is that there were surprisingly high rates of obesity, hypertension and diabetes. These health issues did not affect all people uniformly, however. People living up in the mountains tended to have less obesity and diabetes, while people living in suburban and urban areas tended to suffer more from these chronic illnesses. Although the Global Burden of Disease study is powerful, public health interventions in the developing world must take into account local variations in health pressures and needs.

The aforementioned New York Times piece highlights why some of the shifts in global mortality have occurred, citing things like global vaccination efforts, better education for women and focus on achieving the Millennium Development Goals.

One thing is certain: the global health landscape has changed over the past twenty years, and the new data from the Global Burden of Disease study will be useful in both determining public health priorities and optimizing interventions.

Sunday, December 23, 2012

Alabama: Ending Segregation of Inmates with HIV

wikipedia.org
Here is a nice New York Times article about the recent Alabama court ruling against the state's policy of segregating inmates with HIV from other inmates. This practice is associated with social isolation, stigmatization, lack of access to certain educational programs and an inability to transfer to prisons closer to families. Inmates are forced to wear arm bands identifying them as being HIV positive, eat alone and are not allowed to work around food; another nice New York Times article about this can be found here.

My friend and colleague Dr. Gonzalo Bearman wrote a very nice blog piece about segregating inmates with HIV back in November that is also worth taking a look at.

wikipedia.org
The New York Times article notes that Alabama inmates are not isolated based on having the hepatitis B or C viruses, both of which are more infectious than HIV. All three viruses are transmitted through blood and body fluids. Activities such as having unprotected sex and tattooing (if needles or ink are reused) can lead to acquisition of any of these viruses.

Per the CDC, people who are incarcerated are at increased risk for both acquiring and transmitting HIV. The CDC does not recommend isolating inmates with HIV, however. Rather, the CDC recommends testing inmates for HIV at the time of facility entry and exit, providing educational and treatment programs to inmates who test positive and linking inmates with HIV to care when they are released.

The Alabama court ruling is a definite victory for inmates living with HIV in Alabama. More work needs to be done, however, as this practice of segregation is still in place in South Carolina. Beyond this, prisons and jails should consider adopting practices that will limit infectious disease spread across the board, such as making condoms available.

Saturday, December 22, 2012

Dengue: Already Entrenched in Southern Florida?


Dengue activity over the past 3 months (blue areas = areas of ongoing
transmission risk); www.healthmap.org/dengue
Here is a nice article on the potential for dengue virus to re-emerge in the United States. The article links to a poster presentation by Shin and colleagues from the University of Florida that was presented at last month's American Society of Tropical Medicine and Hygiene annual meeting. These authors isolated a distinct strain of dengue virus from an outbreak of dengue fever in Key West in 2010 and note that this strain may circulate in the region. Only their abstract is available for review so it is not possible to comment on their research further at this time.

Dengue is a viral infection transmitted by Aedes aegypti (and Aedes albopictus) mosquitoes; it is the most common mosquito-borne viral infection. It causes an acute febrile illness characterized by severe pain (which gives the disease its colloquial name: "breakbone" fever). Although not associated with high mortality, the disease is nonetheless associated with significant morbidity.

Aedes albopictus mosquito (one of the mosquitoes
that carries dengue in the United States); cdc.gov
It is worth taking a second to orient yourself to the map that appears at the beginning of this post; this map shows areas of dengue activity over the past three months, and areas of sustained transmission appear in blue. The research by Shin and colleagues begs the question: should southern Florida also appear in blue on this map?

In recent years we have seen outbreaks of dengue in multiple areas of the United States, including Hawaii, Texas and Florida (as noted above). It is possible that climate change, with global increases in mean temperatures, is playing a role in expanding the disease by increasing the geographic range of the mosquitoes that carry the dengue virus.

Anything that can capture rainwater can become a breeding
ground for the mosquitoes that carry dengue (cdc.gov)
Here is an abc news story on dengue in Florida that provides a lot of nice background information on this problem. The article also discusses the use of genetically modified mosquitoes to help control the disease; see here for a previous discussion of this practice.

More examples of potential breeding grounds
for mosquitoes (cdc.gov)
The environment in southern Florida (and many other areas of the United States) can support endemic dengue transmission. To boot, we already have the mosquito vectors that carry this disease (as well as other diseases such as chikungunya). As both of these mosquito-borne viral illnesses have seen geographic expansion in recent years, the medical and public health communities in the US need to be especially vigilant in looking for cases of these diseases and controlling the mosquitoes that transmit them.

Friday, December 21, 2012

Chikungunya: Coming to the United States?

cdc.gov
Could we see chikungunya outbreaks in the United States? According to a modeling study by Ruiz-Moreno and colleagues the answer is yes.

Chikungunya is a viral illness carried by mosquitoes that was first isolated in Tanzania in the 1950s. The name derives from the Kimakonde language and means "to become contorted." Profound joint pain leads to a 'stooped over' appearance, thus the name.

Symptoms of acute infection are nonspecific and are similar to dengue, with fever, headache, nausea, muscle and joint pains and fatigue. Peculiar to this virus, some people can have longstanding joint pain that can last for months, even years. There is no vaccine to prevent this illness and no treatment (other than supportive care).

Global spread of chikungunya virus, 2005-2009 (cdc.gov)
Chikungunya is endemic in Southeast Asia and Africa. In recent years the disease has "emerged" from these areas; in 2005 we saw outbreaks on islands in the Indian Ocean (following an outbreak in Kenya in 2004), with subsequent spread across India. A related outbreak occurred in Italy in 2007, as well.

The mosquitoes that transmit chikungunya (Aedes albopictus, or the "Asian tiger" mosquito and Aedes aegypti) are both present in the United States. If a returning traveler has chikungunya virus in their blood and are bitten by one of these mosquitoes, conceivably that mosquito could transmit the virus on to other people.

The study by Ruiz-Moreno et al, published in PLOS Neglected Tropical Diseases in November, utilized computer modeling to assess if a single returning traveler infected with chikungunya could cause sustained transmission in the United States.

Aedes albopictus (the "Asian tiger") mosquito, one of the
vectors for chikungunya (cdc.gov)
This study revealed that cities with marked seasonal temperature variation (such as New York and Atlanta) have potential for periodic chikungunya outbreaks. In these areas epidemics could occur during the periods in time the mosquitoes are most likely to breed (warmer times of the year). Cities with less seasonal temperature variations (such as Miami) with higher mean temperatures have the potential for sustained epidemics.

Chikungunya is a serious viral illness with the potential for significant morbidity. Since it was first discovered in the 1950s it has "emerged" dramatically, with considerable additional expansion over this past decade. The study by Ruiz-Moreno and colleagues confirms that epidemic potential exists in the United States. The medical and public health communities need to be aware of this potential and vigilant in monitoring for chikungunya cases.

Thursday, December 20, 2012

Congratulations to Audrey Le and Jackie Arquiette!

From left to right: Audrey Le, Drs. Bearman and Stevens,
Jackie Arquiette; in La Hicaca, Honduras, June 2012
Congratulations to Audrey Le and Jackie Arquiette! Both are VCU School of Medicine students who participated on our health brigade to rural Honduras this past June and did research projects on indoor air pollution and the microbiologic and clinical efficacy of our water filter program, respectively. Their research was featured by the VCU News center today.

Administering a survey,
La Hicaca, Honduras
Audrey and Jackie were able to design, conduct and analyze their data within less than one year. Their results will be shared with the local Ministry of Health and community leaders when we return to Honduras in January. Both studies will a have a direct impact on the health of the people we serve.

Fake Malaria Drugs: Driving Resistance and Killing Patients

Anopheles mosquito (the mosquito that carries
malaria) taking a meal
Here is a disturbing NPR report on fake malaria drugs. The article highlights the issue of counterfeit malaria drug use and how this has a negative impact on patients and drives drug resistance.

Malaria, a parasitic disease carried by mosquitoes that destroys red blood cells, is a major cause of worldwide morbidity and mortality (killing over 600,000 people per year).

There is a criminal industry focused on producing fake malaria drugs. As malaria can be deadly (and people can die quickly), this industry directly compromises patients' lives. Some of these false drugs actually contain low levels of active anti-malarial compounds-too low to cure the infection but high enough to allow the parasite to develop drug resistance.

The NPR article links to a study by Newton and colleagues published in 2008. In this study they examined 391 samples of the anti-malaria drug artesunate collected in Southeast Asia and found that approximately 50% contained no or very small levels of this compound. Some of the compounds that were detected were potentially dangerous: these included a carcinogen and raw material for the street drug 'ecstacy.'

This is a problem that extends beyond malaria drugs: as I previously noted, up to 50% of medications in some countries for life-threatening diseases may be fake. A major issue is our poor understanding of the scope of this problem.

The problem of malarial drug resistance is a major one: we only have a few anti-malarial drugs as it stands. If resistance to these compounds becomes more widespread than more patients will die. We need to preserve the drugs we have left, including combating such diabolical practices as creating fake or profoundly substandard anti-malarial medicines.


Wednesday, December 19, 2012

The Dangers of Recreational HIV Drug Use: "Whoonga"

Here is an interesting NPR story of HIV drugs being used as recreational street drugs. Apparently this is a real problem in South Africa, although the issue has not generated a lot of press to date.

People crush anti-HIV drugs such as efavirenz and or ritonavir and mix these together with illicit substances (such as methamphetamine, opiates or marijuana) and smoke the concoction. In South Africa one such mixture is dubbed "whoonga").

Efavirenz can cause neuropsychiatric side effects (things such as vivid dreams). Ritonavir may boost the effect of other illicit substances.

A 2011 article on whoonga use from the BBC provides a nice overview of this problem in South Africa. A nice commentary piece published in the The Lancet Infectious Diseases on the recreational use of HIV drugs by Grelotti and colleagues (and on which the above NPR story was based) can be found here.

A major problem related to recreational HIV drug use is the emergence of anti-HIV drug resistance. HIV is a viral illness that requires multiple different anti-viral medications used in concert to treat effectively. When the virus is exposed to these drugs intermittently or not in combination drug resistance can emerge rapidly. Smoking "whoonga" essentially does just this: exposes people to intermittent levels of single anti-HIV drugs, thus allowing HIV to develop resistance to that single agent. This has serious consequences for the drug user if they are HIV positive, and to entire communities. If an HIV positive whoonga user develops efavirenz resistance, for instance, they can then pass that resistant virus on to another person.

In resource-limited settings sophisticated drug resistance testing is often not available, further complicating the ability to identify patients who have acquired resistance through recreational HIV drug use, or from contact with a recreational drug user.

The article by Grelotti and colleagues also outlines other potential consequences: diversion of HIV drugs, criminal behavior related to HIV drug diversion that can endanger patients and healthcare providers, et cetera. These authors call for more research into this issue and enhanced screening for recreational HIV drug use by clinicians.



Tuesday, December 18, 2012

Space Tourism: Need for Health Screening?

wikipedia.org
Here is interesting commentary on the potential health hazards of 'space tourism.' This refers to people who buy seats on suborbital commercial flights and who will experience zero-gravity and significant "G" forces. There are fears that such stressors could unmask cardiovascular disease (precipitate heart attacks) or other underlying health issues. The article on which the BBC commentary was based can be found here.

I was struck in reading this by the following:

1) Wow! We are talking about commercial space tourism. Although this industry is in its infancy, this seems like the stuff of science fiction.

2) This has to be the epitome of a "first world" health problem! Many people (though thankfully fewer than 20 years ago) are still dying from diarrhea, largely related to poor sanitation (almost 1.5 million died in 2010 alone). In 2010 over 125,000 people died from measles, a disease that is vaccine preventable. In striking contrast to these age-old health problems is the need to develop screening guidelines for commercial space tourists.

An interesting juxtaposition: a seat on a commercial space flight will cost around $200,000 dollars (for a whopping 4 minutes of weightlessness); this is 400 times the per capita GDP of people living in Zimbabwe. In our work in Honduras we support a rural, mountainous community of approximately 2,000 people across 17 villages with locally created clay water filters, each of which can provide clean drinking water to an entire family for approximately 2 years. One space ticket would pay for 8,000 water filters (they each cost roughly $25) and provide 16,000 years of clean drinking water. That's the equivalent of 333 person-years (when average family size is taken into account) of clean drinking water per second of weightlessness.

It will be interesting to see to what extent space tourism 'takes off' as a phenomenon.

Monday, December 17, 2012

A History of Malaria Drugs: In Under 3 Minutes

An Anopheles mosquito (the vector for malaria
parasites; cdc.gov) 
Here is a very nice short video appearing over at NPR on the history of malaria, anti-malaria drugs and increasing malaria drug resistance. If the link above is sluggish the video can also be seen on YouTube. This is well worth taking a look at.

More On the Malaria Vaccine: Q&A with Sir Brian Greenwood

Plasmodium falciparum (malaria) parasites within
red blood cells (cdc.gov) 
Here is a nice Q&A piece with Sir Brian Greenwood on the recently reported (RTS,S) phase 3 malaria vaccine trial.

As previously discussed, malaria is a parasitic disease carried by mosquitoes that destroys red blood cells and is associated with high global morbidity and mortality (leading to over 600,000 deaths per year).

Greenwood provides a nice overview of malaria as well as a brief history of prior malaria vaccine efforts. He also discusses how to interpret the RTS,S trial results and their implication for future malaria vaccine work. Although the RTS,S vaccine does not appear to be as effective as initially hoped, this work does provide hope that an effective malaria vaccine is possible.


Sunday, December 16, 2012

Using HIV Drugs for Staphylococcus aureus Infections?

Staphylococcus aureus (cdc.gov)
Here is an interesting article by Alonzo et al just published in Nature looking at the pore-forming toxin "leukotoxin ED" (LukED) secreted by many Staphylococcus aureus bacteria. Pore-forming toxins create channels in human cells that disrupt cell function and ultimately lead to cell death.

These authors found that a receptor on human T cells, CCR5, which also happens to be a co-receptor for HIV entrance into T cells, is required for LukED activity.

This is interesting in that we already have a drug (maraviroc) used to treat HIV that blocks the CCR5 receptor, thereby disrupting HIV's ability to gain entrance into human T cells. Alonzo et al found that maroviroc disrupted LukED killing of T cells in vitro. These authors used an in vivo model looking at LukED's effect on mice with and without the CCR5 receptor and found mice with the receptor were more likely to die (the implication being LukED cytotoxicity is dependent to a large extent on the CCR5 receptor). 

Not all Staphlococcus aureus isolates harbor the LukeED toxin, and it is not clear if these study findings will translate into real benefits in humans. However, Staphlococcus aureus is a major cause of morbidity and mortality globally, and the above study opens up intriguing new treatment possibilities that may aid in treating these serious infections. More research is warranted. 


Saturday, December 15, 2012

Top 10 Global Health Milestones of 2012

Water filters in La Hicaca, Honduras
It's the time of the year when we start seeing "Best of..." lists. Here is a nice one outlining the "Top 10 Global Health Milestones in 2012." The list links to brief articles on each milestone, from a London summit on family planning to calls for a reinvented toilet to plans for providing HPV vaccine to women in the developing world. A lot of exciting things happened in global health in 2012! These articles are well worth taking a look at.

Friday, December 14, 2012

Combating Neglected Tropical Diseases in Honduras

I had the great opportunity to 'guest blog' today over at the Global Network for Neglected Tropical Diseases' blog on our work to combat neglected tropical diseases in Honduras. The full blog post can be found here.

More Global Health Data! The WHO Global Health Observatory


WHO Global Health Observatory (www.who.int)
More great news for people who love detailed global health data! Christmas really did come early this year.

The World Health Organization (WHO) is making improvements to their Global Health Observatory (GHO), a repository that is billed as "the world's largest and most comprehensive collection of up-to-date health data." Their goal is to provide access to a huge amount of health data (via a single web portal) that is easy to navigate and meaningful.

www.who.int
The site really is terrific; I briefly explored the site this morning to look at updated health data on Honduras (where our public health/ medical program is). The GHO site is easy to navigate and depicts data in an easy to understand, compelling way. The graphics appearing throughout this post were pulled from the site/ linked partner sites.

Rural sanitation
trends, Honduras
(www.who.int)

Under-five mortality rate, Honduras
(www.childmortality.org)


Proportional mortality, Honduras (www.who.int)

Principle causes of death in Guatemala (Honduras data not available) 

Thursday, December 13, 2012

New Insight Into Global Morbidity and Mortality: The Global Burden of Disease Study

wikipedia.org
An incredible amount of data on global mortality and morbidity is now available for free from The Lancet online. These data are from the Global Burden of Disease Study (GBD), a herculean effort sponsored by the Bill & Melinda Gates Foundation.

These data have already generated a significant amount of press (see a nice article in The Washington Post here); this project is simply amazing.

I have to admit I felt like a kid on Christmas morning when I first started going through these articles... there are few things epidemiologists like more than data. And there are a whole lot of data associated with the GBD project.

Here are some things I found notable; my comments mainly focus on Latin America as our medical/ public health project is in Honduras. There is a whole lot more in these data than my comments below reflect so I encourage you to take a look at these articles-they are all available free online.

Deaths due to communicable, neonatal, maternal and nutritional causes dropped from 15.9 million in 1990 to 13.2 million in 2010, a 17% decrease. In contrast, deaths due to non-communicable disease increased by a little under 8 million, accounting for approximately 66% of all deaths. Deaths in children less than 5 years of age dropped a whopping 59% since 1970 (from 16.4 million in 1970 to 6.8 million in 2010).

The male/ female life expectancy in Honduras has gone up from 54.7/ 58.6 in 1970 to 70.5/ 73.2 in 2010. In contrast, the male/ female life expectancy in the US in 1970 was 67/ 74.6 and 75.9/ 80.5 in 2010. There is still a marked discrepancy between 'developed' and 'developing' nations, but significant gains have been made; there are regional and country-specific differences, of course, but overall people are living longer.

The global burden of disease has shifted away from premature deaths and from deaths due to communicable diseases to deaths caused by non-communicable diseases. The top three diseases in terms of disability-adjusted life years ("DALYs") in 1990 were: 1) lower respiratory infections, 2) diarrhea and 3) preterm birth complications. In 2010 these had dropped to #2, #4 and #8, respectively. In 2010 ischemic heart disease was #1 (up from #4 in 1990) and stroke was at #3 (up from #5 in 1990). In terms of DALYs, HIV/AIDS went up dramatically between 1990 to 2010: from #33 to #5.

There were significant regional differences in DALYs attributed to various disease states. For instance, in central Latin America interpersonal violence was the #1 contributor to DALYs, with ischemic heart disease ranking #2. In contrast, in the region including the US interpersonal violence was the 25th highest contributor to DALYs.

Looking across 67 risk factors for 21 world regions there was an overall shift in global disease burden/ morbidity from risk factors promoting childhood communicable diseases to those promoting adult, non-communicable diseases.

In 2010 the biggest DALY risk factors were high blood pressure, tobacco smoking and alcohol use; in most of Latin America the greatest risk factor was alcohol use. Back in 1990 the greatest DALY risk factors were childhood underweight and indoor air pollution from solid fuel use.

These Global Burden of Disease data are absolutely fantastic and provide a comprehensive, methodologically sound global picture of the leading causes of morbidity and mortality and how these have changed over the past twenty years; more importantly, these data can be looked at by country and region. This information should be used by the public health and development communities to target interventions that will have the greatest impact for a given country/ region.

From an overall disease burden perspective, the world is becoming a different place than it was twenty years ago. Our health systems need to adjust to account for a growing population of older people with significant comorbidities such as heart disease, diabetes and osteoarthritis. This is true for both developed and developing countries.

Tuesday, December 11, 2012

Combating Antibiotic Resistance: A Call for Collaboration

Methicillin resistant Staphylococcus aureus (MRSA) (cdc.gov)
Here is a nice op-ed article by Carl Nathan that appeared in Sunday's New York Times. Nathan discusses the problem of antibiotic resistance and the challenges to new drug development, including bacteria that rapidly develop resistance to new antibiotics and poor economic incentives for industry to create new drugs.

Nathan highlights novel collaborations between industry, government and the non-profit sector designed to expedite new drug discovery. The Infectious Diseases Society of America has great information on the problem of antibiotic resistance (and potential solutions) that can be found here.

Monday, December 10, 2012

Antibiotic Use in Cattle: Driving Antibiotic Resistance in Humans?

wikipedia.org
Here is a nice article published yesterday in the Kansas City Star that discusses antibiotic use in cattle and its potential effect on antibiotic resistance in humans. I have alluded to this connection in several previous posts; this article provides a comprehensive and balanced overview of this problem. 

Some highlights (my comments appear in italics):  

1) 80% of all antibiotics are used in animals; as antibiotic resistance in large part is related to the selective pressure of antibiotics on bacteria, efforts to combat resistance in humans have to account for the huge amount of antibiotics used in animal husbandry 

2) The beef industry can now bring a calf to slaughter in a little over a year, half the time this process used to take (this is attributed to genetics, antibiotics, growth promoters and hormones); see yesterday's post for comments on how antibiotics may be related to the obesity epidemic in humans

3) Antibiotic resistance in animals has been linked to human illness

4) There are significant barriers to addressing this issue

As outlined in this article, this is a complicated issue. However, to avoid entering the 'post antibiotic era' we need to aggressively preserve the antibiotics we have left-which means using them judiciously in both humans and animals. Articles such as this that raise awareness and provide balanced information are crucial. 


Sunday, December 9, 2012

Obesity on the Rise: Related to Antibiotic Use?

Here is a nice NPR piece on the possible link between childhood obesity and antibiotics. This story is from back in August but I figured I'd bring it back up in case anyone missed it; I also alluded to this in an earlier post.

Obesity has become epidemic in the United States. According to the CDC, the prevalence of obesity has exploded over the past few decades: almost one in five children and adolescents (17%) is now obese, as well as over one-third of adults (36%). The obesity prevalence in children has nearly tripled since 1980.

Here is an instance where 'a picture is worth a thousand words.' The following maps illustrate obesity prevalence in US adults in 1990 versus 2010:
These maps are both compelling and disturbing; what has caused the explosion of obesity over the past twenty years?

An intriguing question is whether the increase in obesity prevalence is related to antibiotic use.

Antibiotics have long been used in animal husbandry to "fatten up" food animals. It is not exactly clear why this happens (e.g., why using low levels of antibiotics leads to fatter animals). An important question is whether antibiotic use also drives a similar process in humans.

A study by Cho and colleagues that was published in Nature in August found that the administration of antibiotics to mice was associated with changes in the composition of organisms in the gut that led to changes in fat metabolism and fatter animals. Although this was a mouse model, it does provide 'biologic plausibility' for how antibiotic administration could lead to obesity in humans.

Another article by Blustein and colleagues utilized a database from the UK with data from over 11,000 children born in 1991-1992. These authors found that antibiotic exposure within the first 6 months of life was subsequently associated with increased body mass from 10-38 months of age.

Although the above studies are intriguing, they do not provide definitive evidence that the current obesity epidemic is related to antibiotic exposure. Many things are likely contributing to this epidemic; one thing is clear, however: the prevalence of obesity has increased dramatically and this has had-and will have-enormous implications for our healthcare system and society.

Antibiotics have revolutionized modern medicine: they are critical for helping patients survive cancer therapy, for many complicated surgeries and are life-saving in the setting of many serious infections. However, studies such as those noted above illustrate that antibiotics may have effects beyond their intended purpose, and is further evidence that their use should be targeted and judicious. This is even more important given the widespread problem of antibiotic resistance and the paucity of new antibiotics that are being developed. More research into the link between obesity and antibiotic use is needed.




Saturday, December 8, 2012

Pertussis on the Upswing in the United States: What Can Be Done?

Here are the most recent numbers from the CDC on pertussis infections in the United States.

Bordetella pertussis (cdc.gov)
Pertussis, a respiratory illness also known as "whooping cough," is caused by the bacteria Bordetella pertussis and is a highly contagious disease. The disease is spread from person to person by coughing and sneezing. In adults, the disease usually begins with cold-like symptoms, with the disease later characterized by fits of severe coughing; disease can go on for months and is sometimes referred to as the "100 day cough." Violent coughing episodes lead to a paucity of air in the lungs, with the "whooping" sound thereafter generated by rapid inhalation; listen here for what this sounds like.

Pertussis is associated with significant morbidity in children, adolescents and adults, but can be fatal to younger children, especially infants. Infants can develop apnea (long periods of not breathing) and die from this illness; over 50% of infants less than 1 year of age who develop pertussis need to be hospitalized.

Pertussis is common in the United States, and periodic spikes in cases are seen every 3-5 years. The last spike was in 2010 where there were 27,550 cases reported; we thereafter saw a decline in cases in 2011. We have seen a spike in cases in 2012, with over 36,000 cases reported to the CDC by November 17th with 16 deaths. Some states (such as Washington, Minnesota, Vermont and Wisconsin) have been hit particularly hard; see the table below.

cdc.gov
Although good vaccines are available for pertussis (and are included in the standard childhood vaccination program in the United States), by late childhood immunity from these can wane thereby leaving older children, adolescents and adults at risk for developing the disease. This waning immunity is partly responsible for why the disease is still common. Additionally, as the initial symptoms are non-specific, the disease is often not recognized until late (if at all), with an infected person transmitting the infection on to others.

So what can be done? The most important thing is for people to be immunized against pertussis; if people don't contract the disease then they won't spread it to others, especially the population most at risk for disease complications: infants.

A booster of pertussis is recommended for children at 11 to 12 years of age and for all adults (this is the "Tdap" vaccine). Adults should receive a one-time Tetanus-Diphtheria-Pertussis vaccine ("Tdap") and can do so regardless of when they received their last tetanus shot. As infants are at particularly high risk for having severe disease with pertussis, families of young infants (including pregnant women) should make sure they have received the Tdap vaccine. More information about pertussis vaccination can be found here.




Friday, December 7, 2012

Update on Yellow Fever Outbreak in Darfur

Yellow fever risk area in Africa (cdc.gov)
Here is an update from the WHO on the yellow fever outbreak in Darfur.

"Yellow fever" refers to the disease caused by the yellow fever virus that is transmitted by mosquitoes in areas of Africa and South America. This a hemorrhagic fever virus associated with substantial mortality and high morbidity. Worldwide there are approximately 200,000 cases yearly with 30,000 deaths. Although a safe and effective vaccine is available for this disease, there is no treatment (other than supportive care) for people who contract it. 

Yellow fever virus (cdc.gov)
As of December 4th in the Darfur outbreak there have been 732 suspected cases of yellow fever with 165 deaths.

A multi-disciplinary team is investigating the outbreak to better understand its scope and epidemic potential. War and social upheaval have traditionally been linked to infectious disease outbreaks. Recent conflict and mass population displacement in Sudan likely has contributed to this current outbreak. 

An emergency mass vaccination campaign has been occurring in the region since late November; the goal is to vaccinate over 3 million people at risk for acquiring the disease. This vaccination effort will be critical in curbing this outbreak and preventing a full-blown epidemic. 
Aedes aegypti mosquito (the mosquito that transmits
the yellow fever virus); cdc.gov

Thursday, December 6, 2012

Malaria Vaccine Report: Hope on the Horizon?

Where malaria occurs (cdc.gov)
Here is a study recently published in the New England Journal of Medicine on the "RTS,S/AS01" vaccine against malaria.

Malaria, a parasitic disease carried by mosquitoes that destroys red blood cells, is still a major cause of worldwide morbidity and mortality (responsible for over 600,000 deaths per year) and an anti-malaria vaccine has been seen by many as the 'holy grail' of public health.

This study follows up one published in 2011 that noted a vaccine efficacy of 45% (95% CI 23.8-60.5) for severe malaria in children aged 5-17 months. The current trial looked at vaccine efficacy for children 6 to 12 weeks of age and found a much lower (not statistically significant) efficacy of 26% for cases of severe malaria in the intention-to-treat analysis (95% CI -7.4 to 48.6). 

Malaria parasites in red blood cells (cdc.gov)
Why the difference in efficacy between the two age groups? The authors posit the lower efficacy rate in younger children may have been due to a less mature immune system or to co-administration with other vaccines. 

Why has creating a malaria vaccine proved so elusive? In a nice editorial that accompanies the above article, Johanna Daily outlines some of the challenges we have encountered to date in creating a malaria vaccine. These include malaria's long coevolution with humans, which has produced a robust parasite that is adept at avoiding destruction by our immune system, as well as an incomplete understanding of our immune response to the organism (which would provide insight into vaccine development). 

Of note, malaria is another organism where drug resistance is a major problem. Given the serious, life-threatening nature of malaria infections, and the paucity of drugs available to treat these, malaria drug resistance is a major global problem. 

Although the RTS,S/AS01 vaccine does not appear to be "ready for prime time," it does provide hope that an effective malaria vaccine can be produced. Given the global morbidity and mortality associated with this disease, continued intense research into malaria vaccine development is warranted.