Update on Human H7N9 Avian Influenza Cases in China

VCU Global Health & Health Disparities Program (GH2DP)
group entering Honduras during the H1N1 pandemic, 2009

Here is the latest update from the WHO on human H7N9 avian influenza cases in China; as of April 5 16 patients have laboratory-confirmed infection (up from just 3 a few days ago) and 6 have died. Contacts of the people who are infected are being closely watched for signs and symptoms of respiratory infection; to date no clear evidence of person to person transmission has been found.

Although it not clear yet where people acquired H7N9, the virus has been detected in pigeons in a major Chinese agricultural market, leading to the mass execution of 20,000 birds.

Here is an April 4th health advisory on H7N9 from the CDC and an April 5 'telebriefing' with the CDC's director Dr. Tom Frieden. Here is detailed, specific travel advice from the CDC for people going to China (emphasizing such things as avoiding live bird and poultry markets, practicing good hand hygiene, et cetera).

Much is unknown about the epidemiology and transmissibility of the H7N9 virus; to date it does not look efficient in terms of person to person transmission, which is the public health community's greatest concern. One thing is certain: these new human cases of "bird flu" illustrate how quickly novel infectious disease threats can emerge, and we must be vigilant and act quickly as a global community to identify, contain and development treatments for these diseases when they appear.

New Article on Zombies Published in Emerging Infectious Diseases

cdc.gov

Here is an interesting article that was just published in Emerging Infectious Diseases on the use of the public's general fascination with zombies for public health education.

The article refers to back to an earlier CDC blog post that used a "zombie apocalypse" as a vehicle for educating about disaster preparedness. I definitely remember when this clever 2011 CDC blog post was published, and the general content of the message. I have to admit that I can not recall any other general disaster preparedness messages delivered by the CDC or any other group... perhaps there really is something to tying health messages to fictional, highly memorable content?

The current Emerging Infectious Diseases article provides both historical background information on zombies as well as information on their popularity across a variety of media/ entertainment platforms (books, films, video games, et cetera).

The article discuss how public health messages that pull from fictional depictions of zombies could be used to educate about such real-world issues as infection control, risk for bioterrorism, disaster preparedness, provide a framework for ethical discussions, et cetera.

The authors provide a real-world example of the mass killing of 50,000 or so dogs in Bali in 2008 in an effort to control a rabies outbreak; this led to a discussion about the most optimal, ethical, control of rabies in a given area (e.g., mass killing versus vaccination). The authors of the Emerging Infectious Diseases article posit that ethical dilemmas depicted in fictional dramas (such as those involving zombies) can help provide a relatable framework for real-life infection control and infectious diseases issues.

Anyway, I am going to stop blogging now so I can go work on my emergency kit/ plan; you never know.

Three Human Cases of Avian Influenza A (H7N9) Reported in China

Photo credit: Dr. Gonzalo Bearman

Here is an alert from the World Health Organization on 3 H7N9 avian influenza cases ("bird flu") discovered in China. Two cases were reported in Shanghai with another case reported in Anhui province. Patients presented with respiratory infections that progressed to severe pneumonia between February and March 2013; 2 of these patients have died.

Investigation into these cases is ongoing; to date, there has been no evidence that person to person transmission has occurred.

Avian influenza A viruses do not typically infect people, although cases have been reported. When human infection occurs, it is usually in people who have been in close proximity to infected poultry. To date, human to human transmission of avian influenza has been rare.

There is always concern with influenza that viruses circulating in animals (such as birds) will "jump" to humans, combine with human strains and create new influenza strains that we, collectively, have little or no immunity to. This phenomenon led to the 1918-1919 global influenza pandemic that killed between 20 and 40 million people. This is why we must continue to be vigilant in monitoring for cases of human infection with animal influenza strains, such as H7N9 avian influenza.

A Cure for HIV?

Mural in Brussels

Here is a remarkable study by Sáez-Cirión and colleagues that was published this month in PLOS Pathogens. These authors looked at a group of 14 patients with HIV who received treatment early during infection and were able to maintain viral suppression even after coming off HIV medications. 

Historically, there has been controversy over when to start combined antiretroviral therapy (cART) for the treatment of HIV. Traditional arguments against starting cART early in infection included concern over possible long-term medication toxicity, cost and the development of drug-resistance. Arguments for early cART initiation include preserving immune function, reducing host viral reservoirs and limiting chronic immune activation. The study by Sáez-Cirión et al outlines another potential benefit: it is possible early therapy can lead to a "functional" HIV cure. 

Antiretrovirals have literally been life-saving to people living with HIV. Although these drugs suppress viral replication and allow for some amount of immune system recovery, in the vast majority of patients viral rebound and consequent immune system deterioration will occur rapidly once the drugs are removed. There are a small subset of patients (less than 1% of all HIV positive patients) who are, by virtue of gene differences, able to control the HIV virus to levels normally only achieved with cART (these patients are known as "HIV controllers"). 

Sáez-Cirión and colleagues examined a group of 14 patients who were discovered to have HIV very early in their infections and who were provided cART, and later came off cART. These patients behaved very much like "HIV controllers," although they did not have the gene distinctions that allow that group of patients to control HIV. As opposed to the typical scenario (where rebound viremia occurs quickly after cART cessation), these 14 patients demonstrated long-term viral suppression even off cART. These patients were dubbed "post-treatment controllers." The authors estimate that (among patients who are treated early in HIV infection) approximately 15% of patients receiving early HIV therapy may ultimately go on to have long-term viral suppression off cART. 

Although (early) post-treatment control of HIV does not truly represent a cure, for patients who benefit from this phenomenon this may represent a "functional" HIV cure. More study needs to go into this phenomenon and its implications for widespread HIV treatment and policy: will this phenomenon maintain over decades (not just years)? What are the implications of this for vaccine development? Certainly this implies that the immune system can be primed to efficiently control HIV: how can we capitalize on this via vaccination? How can we best identify patients with early HIV infection and get them into care immediately? What about the 85% of HIV positive patients who do not behave like post-treatment controllers?

The article by Sáez-Cirión and colleagues only further tips the scales in favor of early treatment. Antiretroviral drugs have become safer and easier to tolerate over the past decade, and as a result compliance with cART regimens has been easier to maintain. Recommendations for cART initiation have now fully shifted towards early therapy (see the most recent US national HIV treatment guidelines here), with therapy now recommended for all HIV positive patients regardless of immune status. With these new data implying that upwards of 15% of patients may be able to achieve a functional HIV cure with early cART initiation, identifying these patients early and getting them into care is more imperative than ever. 

VCU Medical Student Presents on Satisfaction with Brigade Care at CUGH Annual Conference

Kate Pearson, presenting at the Consortium
of Universities for Global Health's Annual
Conference, Washington, DC, March 14, 2013

Congratulations are in order to Kate Pearson, a third year VCU medical school student who presented her research on satisfaction with short-term medical brigade care at the Consortium of Universities for Global Health's annual conference in Washington, DC, yesterday.

Kate surveyed patients who received care at the Honduras Outreach Medical Brigada Relief Effort (HOMBRE)/ VCU Global Health and Health Disparities Program (GH2DP) clinics in the Department of Yoro, Honduras, in 2011. Her survey was a pilot project designed to identify key areas where we can improve the care we provide on our annual medical relief trips, as well as identify areas where we can bolster our health education efforts.

Twenty-three surveys were collected. Although the majority of patients noted satisfaction with the care provided, the survey helped to identify some key areas for future improvement. The majority of patients (70%, 16/23) desired more frequent clinics (2-3 times/ year), and the following were noted as areas to provide more health education: water purification (68%, 15/23), dental care (61%, 14/23), mental and emotional health (52%, 12/23) and nutrition (52%, 12/23).

Kate's data will help us target our health education messages on our upcoming May-June 2013 brigade, and will serve as a platform for a larger survey that will help us improve the care we provide.

Great work Kate!

The "Superbug" Problem: What Does the CDC's CRE Report Really Mean?

The Great Wave off Kanagawa (wikipedia,
Library of Congress)

Hi everyone! I am back after a long hiatus (vacation and lots of time on the medicine wards/ infectious disease consult service).

I was interviewed this morning by a local radio program about the "Superbug" problem and antibiotic resistance (you can find the interview here, if interested).

This interview was requested, in part, by the recent CDC report on carbapenem-resistant Enterobacteriaceae ("CRE"), and the media coverage that has followed the release of this disturbing report.

Enterobacteriaceae are a group of organisms that typically inhabit the gastrintestinal tract. They are a major problem, especially in hospitals, where they can cause urinary tract infections UTIs), bloodstream infections and wound infections.

CRE are extremely antibiotic resistant bacteria; in some cases these bacteria are resistant to all known antibiotics. Carbapenems are a class of antibiotics often reserved for the sickest, most unstable patients; unfortunately, for CRE, these agents do not work. Not surprisingly, CRE infections have been associated with very high mortality (upwards of 50%). In the case of many of these infections we truly are realizing the "post-antibiotic era," and a return to pre-20th century medicine.

The CDC report notes that during the first 6 months of 2012 nearly 5% of all hospitals reporting on healthcare-associated infections (in this case, UTIs and bloodstream infections) reported at least one CRE infection. When broken down by hospital type, a whopping 17.8% of long-term acute care hospitals reported one of these infections (almost 1 in 5 of all such facilities!). Overall, comparing data from 2001 and 2011, the percentage of Enterobacteriaeceae that were carbapenem-resistant (e.g, CRE) went from approximately 1% to 4%. Looking at one of these organisms in particular (Klebsiella) resistance went from 2 to 10%!

The reality in 2013 is that a person can be admitted to the hospital for a hip replacement, develop a UTI with CRE, and die from the UTI because there are no effective antibiotics to combat the infection. Unless we act now, and decisively, as a society/ global community, we truly are at risk of entering the post-antibiotic era.

In reading about this issue the CDC has some terrific information. For the best commentary I have seen I refer you to the posts over at Controversies in Hospital Infection Prevention.

Only time will tell whether we have the collective wisdom and will to preserve the antibiotics we have, develop new drugs and curb the emergence of antibiotic resistance. If the looming problem of pan-antibiotic resistant organisms is a tsunami, let us have the wisdom to heed the warning of the CDC's CRE report, and get to high ground. As it stands, I fear we will collectively be asleep in bed when the wave breaks.

Are We Entering an Era of Untreatable Gonorrhea?

Here is an excellent article on the growing problem of multi-drug resistant gonorrhea that was recently published in the CDC's Morbidity and Mortality Weekly Report (MMWR).

"Gonorrhea" refers to infection with the bacterium Neisseria gonorrhoeae and is a common sexually transmitted disease (over 300,000 cases were reported in the United States in 2011). Gonorrhea can cause significant morbidity: infertility, ectopic pregnancy, infection can facilitate HIV transmission, et cetera. One of the challenges in addressing gonorrhea as a public health problem is that many people who are infected have no symptoms; despite being asymptomatic, these individuals can still transmit the disease on to others.

Prevalence of ciprofloxacin resistance in urethral gonorrhea
isolates in US men, 1990-2007 (source: cdc.gov, MMWR)

Antimicrobial susceptibility results are not commonly available to clinicians who manage these infections. The infections, once identified are usually treated empirically with antibiotics known to be active against the bacterium. The challenge with this approach is that the organism has acquired resistance to the various antimicrobials we use to treat it. For example, we use to use flouroquinolone antibiotics to treat gonorrhea, but these antibiotics are no longer recommended due to high levels of fluoroquinolone resistance (see the graph above).

We currently are using cephalosporins (such as cefixime and ceftriaxone) to treat these infections, although resistance data is now suggesting that we are seeing some resistance emerge to these agents, as well. The problem here is that if we lose the cephalosporins there are no reliable alternative drugs we can use for these infections.

The authors of the MMWR report highlight the need to ramp up gonorrhea prevention efforts, to screen high-risk patients for gonorrhea "at least annually," to treat patients with appropriate doses of antimicrobials (per the CDC guidelines), and for clinicians to be vigilant in looking for cases of resistant gonorrhea.

Antibiotic Use Driving Resistance on Chinese Pig Farms

Here is a nice article from Time reporting on a recently released study by Zhu and colleagues that was reported in the Proceedings of the National Academy of Sciences (PNAS); this study looked at the presence of antibiotic resistance genes in the soil near 3 large Chinese pig farms.

These researchers found 149 different genes encoding antibiotic resistance, some of which were present at levels 192 to 28,000 times higher than control samples.

The Time article goes on to frame the problem of antibiotic use in the animal industry: 

1) In the United States, 4 times the amount of antibiotics that are used in humans are used for animals, many to treat otherwise healthy animals to promote growth

2) It is not clear to what extent this occurs (using antibiotics to promote animal growth-not expressly to treat sick animals)

3) Antibiotic resistance that develops in animals is a problem for humans-resistance genes can be carried in fertilizer, washed into rivers, et cetera. I previously touched on this in a blog about contaminated pork products and in another blog post about antibiotic use in cattle.  

See here for a link to an excellent perspective article on why antibiotic resistance matters, and what can be done to prevent entering a "post-antibiotic era." It has been well under 100 years since antibiotics were discovered and went into widespread use, and already we are seeing infections emerge that are completely resistant to all of the antibiotics in our arsenal. To a large extent this is due to the selective pressure of antibiotics on microorganisms. 

In order to secure a future in which we still have antibiotics to treat infections, we need to decrease antibiotic selective pressure on microorganisms wherever appropriate. This includes utilizing antibiotics judiciously in the animal growth industry; as mentioned in the Time article, we don't even know the scope of the problem. It is clear that we must act decisively, and concertedly, to address the problem of antibiotic resistance.  

Chagas Disease: A Major Issue in the Americas

The "kissing bug" that transmits
Chagas disease 

Here is a brief NPR piece on Chagas disease. Chagas disease is one of the neglected tropical diseases, and is an insect-borne parasitic infection that affects people in the Americas, especially parts of rural Latin America.

The insect vectors for the disease are known as "kissing bugs." They live in the walls and roofs of houses made of adobe, mud, straw and thatch, and emerge at night to feed on people's faces (I am not making this up). The insects thereafter defecate and the parasite (Trypanosoma cruzi), which is in the stool, gets inoculated through the skin when a person scratches.

Town of La Hicaca; this is one of the sites where we see
patients in Honduras; Chagas disease is a major problem in the area

It is estimated that 11 million people are currently living with this infection, and untreated these diseases persist for life. Chagas disease is associated with major morbidity: over time the infection can lead to heart failure and death from arrhythmias, as well as dilatation of the esophagus and colon with attendant gastrointestinal issues.

Where we practice in rural Honduras Chagas is a major issue. One of our projects for our upcoming May-June trip is administering a survey to assess people's risk for developing the infection, and their knowledge and understanding about how to prevent these infections.

Another nice article on Chagas from the New York Times can be found here.

Fecal Transplantation for Clostridium difficile Infections

Here is a nice interview a local TV station did with my friend and colleague Dr. Michael Edmond about using fecal transplantation to treat Clostridium difficile infections.

Clostridium difficile ('c dif') are bacteria that can cause diarrheal disease; a major risk factor for developing infections with these bacteria is previous antibiotic exposure. In the presence of antibiotics, these bacteria have the opportunity to outcompete the gut's normal bacteria, take over, and cause disease. These infections are associated with significant morbidity, and can be deadly, as well.

Although antibiotics can be used to combat these infections, some people suffer from recurrent infections despite antibiotic treatment. Fecal transplantation replaces the normal bacteria that are lost, and has been associated with high cure rates for patients who have failed other therapies.

The above video is well worth taking a look at.