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.

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. 

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.

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.

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

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. 

Update on Novel Coronavirus in the Middle East

Arabian peninsula (wikipedia.org)

Here is the WHO update on the new coronavirus that was recently discovered in the Arabian peninsula. What is concerning is that this novel coronavirus, known for now as "hCoV-EMC," is (distantly) related to the Severe Acute Respiratory Syndrome (SARS) coronavirus that caused a worldwide outbreak in 2003 with 8,098 cases and 774 deaths. With the hCoV-EMC virus all patients have been severely ill with acute respiratory disease; there have been 9 confirmed cases with 5 deaths as of November 30th.

The earliest reports of hCoV-EMC infection came from 2 retrospectively identified cases in Jordan in April of 2012. Cases have also been identified in Qatar and Saudi Arabia. Across the 9 confirmed cases there have been two "clusters" of infections, raising concern about human-to-human transmission or a common source of exposure.

SARS coronavirus (cdc.gov)

At this point we do not know how this virus is transmitted or what its natural reservoir is. Unlike the SARS virus, it does not appear to easily transmit between people.

We do know that patients with hCoV-EMC present with severe respiratory disease and the virus has been associated with high mortality. Vigilant surveillance of patients presenting with acute respiratory disease and unexplained pneumonias is needed, especially patients in (and with recent travel to) the Middle East.

SARS coronavirus (cdc.gov)

This infection is another reminder that new infectious diseases will continue to "emerge," and the medical community needs to be ever vigilant in identifying these early.

HIV: Learning From Stigmatization

wikipedia.org

Here is a thoughtful piece from over at PLoS on the stigma associated with various infectious diseases, especially HIV. Despite decades of research and education, discrimination still exists for people living with HIV; Gorman cites examples of people denied employment, of HIV positive inmates being isolated from other inmates and the ban on people with HIV entering the United States that was only lifted in 2009.

She poignantly notes that discrimination leads to false beliefs about disease transmission that in turn drive the stigma associated with disease. She also notes that stigmatization is a not a phenomenon isolated to HIV, but rather has been associated with many infectious diseases throughout history. Stigmas alienate people and undermine disease detection, prevention and treatment efforts.

Gorman calls for research into what drives stigmatization, with a special focus on what we can learn from history. As the emergence of new infectious diseases is a reality of human existence, learning from the stigma associated with HIV and other infectious diseases is critical.

Ebola Outbreak: Not Due to Witchcraft

Here is the most recent WHO update on the Ebola outbreak in Uganda; as of November 28 there were 6 confirmed and 1 probable case (case numbers have been adjusted from those previously reported due to testing coming back negative from several patients). There have been 4 deaths. 

One of the key challenges with managing the outbreak has been the belief in some communities that deaths have been due to witchcraft and not Ebola. This reminds me of a poster I saw in a clinic in rural Kenya back in 2001: 

http://ihm.nlm.nih.gov/images/C02494

In many traditional African cultures disease is seen as having a supernatural origin or component, and  witchcraft is believed to play a major role in disease acquisition. Such beliefs can compromise disease prevention efforts. Traditional beliefs wherein HIV is considered to be spread via witchcraft have been associated with higher risk sexual activity (such as not wearing condoms), for example. 

At an herbal medicine shop, South Africa (author's photo)

The WHO report notes working with local religious leaders and traditional healers to facilitate good infection control practices that will help halt the spread of Ebola. Understanding how disease is perceived by a given community and close integration with local health leaders is critical in addressing any health issue, especially one as deadly as Ebola. 

Antibiotic Resistance: Effect of Length of Therapy

Here is a nice blog piece over at PLOS that provides a nice commentary on the problem of antibiotic resistance in people, and discusses the possible relationship of duration of antibiotic therapy and the emergence of resistance. 

In terms of antibiotic therapy length, this is dependent on the condition (e.g., pneumonia, urinary tract infection, et cetera), person-specific factors (does the infection involve the bladder only? does it involve the kidneys? are there bacteria in the blood?) as well as the specific infecting bacteria. A physician needs to take all of these factors into account when recommending an antibiotic treatment course. 

What is clear is that clinicians should follow consensus guidelines when determining length of therapy for a given patient, that non-bacterial infections should not be treated with antibiotics, and that more studies are needed to assess the optimal length of therapy for many bacterial infections.