|Infectious Diseases Discussion
Posts from April, 2012
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|Bacteria on High
I have always appreciated that humans appeared on the scene well after bacteria had established their foothold on earth. We all need to realize that we share the world with these microorganisms and that for many reasons we can not live a sterile existence when it comes to our interacting with the bacterial world. Now, researchers from Georgia Institute of Technology and NASA have made a remarkable discovery. Sampling the atmosphere at the highest levels (troposphere), these investigators have catalogued an incredibly diverse microbiome in earth’s upper atmosphere. Seventeen separate taxa were identified, many of the bacteria having an aquatic origin on earth. Most interesting, samples were obtained over 2 different hurricanes and the investigators found that there was a change in the bacterial communities identified during these storms. One potential ramification of this work is the identification a possible mode of spread of bacterial pathogens from one place to another. This remains to be proven, however. A more likely scenario is the role of these bacteria in metabolism of compounds in the troposphere, including the life cycle of clouds, formation of ice crystals, and overall effect on climate. This study is a nice foundation upon which additional research should shed considerable light on possible additional roles of bacteria in our environment.
Posted by DrSugar on 01/29/2013 at 4:37 PM
|Pneumococcal Vaccine Recommendations
With the release of a new pneumococcal vaccine preparation, deciding who to immunize and how to immunize them has become a bit more complicated. In the following essay, Dr. Scully sorts this all out.
New recommendations for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in immunocompromised adults have been published in the MMWR.1 This includes patients over the age of 19 with problems such as HIV, malignancies, leukemias, and patients on immunosuppressive drugs or with functional or anatomic asplenia. Before the 7-valent conjugate vaccine (PCV7) as added to routine childhood immunization in 2000, Streptococcus pneumoniae was estimated to cause over 17,000 cases of invasive pneumococcal disease (IPD), including 800 cases of meningitis and 200 deaths.2 But the routine use of PCV7 essentially eliminated IPD due to vaccine serotypes, not only in children but also in adults (herd immunity). Although the subsequent years saw an increase in IPD due to non-vaccine serotypes (replacement strains) there was none-the-less a significant overall decline in IPD in both children and adults. In 2010, PCV13 replaced PCV7 in the routine childhood schedule and includes serotypes like 19A that had emerged post PCV7 use and was the cause of multi-drug resistant otitis media.
The thought now behind the use of PCV13 and the pneumococcal polysaccharide vaccine (PPSV23) in immunocompromised adults, is that the combination of the two vaccines will provide better coverage than either one of the vaccines could achieve on their own. The recommendations are divided into vaccine naïve patients and those previously vaccinated adults.
Here’s how it goes:
If a patient has yet to be vaccinated with any pneumococcal vaccine, PCV13 should be initiated first, followed by PPSV23 at least 8 weeks after PCV13. Another dose of PPSV23 can then be given 5 years later. For those who received PPSV 23 before the age 65 for any indication, they should receive another dose of the vaccine at age 65 years, or later if at least 5 years have elapsed since the previous PPSV 23.
For patients previously immunized with one or more dose of PPSV23, PCV13 can be given at least 1 or more years after the last PPSV23. For patients needing additional doses of PPSV23 according to previous guidelines, the next dose of PPSV23 should be at least 8 weeks after PCV13 and at least 5 years since the most recent PPSV23 dose.
Not exactly an easy schedule to remember if you ask me. I assume we’ll get used to it, and just when we do, the ACIP will likely change it again!
The PCV13 vaccine was licensed in December 2011 for adults over age 50 and previously licensed for ages 6 weeks to 6 years of age. So the use of the vaccine in patients aged 19-49 with immune compromise will technically be “off label” use of the vaccine until that formal approval comes through.
So far, the use of the PCV13 vaccine has been well received by my patients and without any adverse side effects. Remember though these new recommendations pertain only to immune compromised adults.
Mary-Louise Scully M.D.
1. CDC. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccines for Adults with Immunocompromising Conditions: Recommendations of the ACIP . MMWR 2012;61 (40):816-819.
2. CDC. Direct and Indirect Effects of Routine Vaccination of Children with 7-Valent Pneumococcal Conjugate Vaccine on Incidence of Invasive Pneumococcal Disease – US- 1998-2003. MMWR 2005;54(36):893-897.
Posted by DrSugar on 12/17/2012 at 11:28 AM
|Moving towards a cure for HIV-Dispatch from ID Week
In the world of cutting edge HIV research, exciting things are happening. Researchers are beginning to think in
terms of curing this previously uncurable pathogen. This week at ID Week in San Diego, we heard
about strategies for this. The Berlin patient, published in NEJM recently, served as a proof-of-concept that the virus could be eradicated. This patient underwent BMT and has been cured 5 years out. This approach though, is not viable for the millions around the world suffering form this plague. The Berlin patient had severe graft-versus-host disease, a life threatening complication of BMT. Also, the cost is prohibitive for large-scale interventions. We heard today about limited stem cell transplantation in which patients have no detectable virus in the blood a year after therapy, even when tested with assays that measure only one copy of the virus in a mL of blood. These patients are still taking antivirals to be on the safe side though. Current antiviral use for HIV has been shown in a landmark study, HPTN 052, to reduce the risk of transmitting the virus by 96%, an astonishing number. This was named Science Magazines top science breakthrough of 2011. With wider rollout of HIV therapies globally, the potential to sustain transmission should drop.
Extensive research is exploring ways to activate the latent T cell reservoir of HIV, so that latent virus there is expressed and then the cells would be susceptible to antiviral medications. This T cell reservoir is felt to be the main impediment to a cure, a sort-of Trojan horse in the immune system. A chemotherapy drug, vorinostat, used to treat cutaneous T-cell lymphoma is in trials to see if it can help deplete this reservoir. It is a member of the class of agents called histone deacetylase inhibitors (HDAC) that work by leading to acetylation of histones that then unwind DNA around them, activating transcription. Early trial results are very promising, demonstrating activation of this pool.
Equally impressive is the progress in antiviral drug development. We heard today about injectible fusion inhibitor drugs that may have to be given only once every 6 months, and long acting oral medications dosed only once every 1-3 months. Combinations of these pills are being tested now in clinical trials. One can imagine the potential that treating patients globally with occasional oral doses and sub-q injections creates. These drugs may offer uses in HIV prevention for high-risk persons, or therapy for those already infected.
D. Fisk - reporting from ID Week in San Diego 10/17-21/2012
Posted by DrSugar on 10/29/2012 at 11:17 AM
There are many species of Mycobacteria in addition to Mycobacterium tuberculosis, the bacteria that causes tuberculosis. M. leprae is the cause of leprosy and there are several dozen different species that live in our environment and to which we are constantly exposed. The group that is the subject of today’s essay is Mycobacterium avium-intracellulare, also known as MAI or MAC (short for Mycobacterium avium complex).
Mycobacteria are divided into several different groups using a variety of criteria. For example, there are the rapid growers, where colonies show up in the laboratory within about 7 days or so and the slow growers, which can take a month or more to show up on agar plates.MAI is in this latter group. A complementary system of identification uses the formation of chromogens or color substrates when the organisms are grown in the light or the dark to help distinguish the organisms from one another. In this scheme, MAI are non-chromogenic, that is they do not form colored colonies in the light or the dark.
These bacteria grow in our environment and naturally live in the soil, water and can be recovered from animals and food. If living in water, they can be aerosolized and can then be breathed into the lungs. If there are abnormalities in the anatomy of the lungs, the bacteria can cause disease. Perhaps the most common anatomical abnormality that predisposes to MAI infection is bronchiectasis, or pathological dilatation of the airways, especially the smaller airways within the lungs. Showerheads and jacuzzi like tub jets can easily aerosolize bacteria and create particulates that are easily inhaled deep into the lungs where they can be deposited. If the person who inhales these particles is predisposed to becoming infected with the bacteria, because of the presence of immunosuppression or bronchiectasis, these bacteria could start to replicate and possibly cause disease. Immunological evidence for the exposure to people to MAI is most frequent in the southeast of the US and the Gulf coast states.The easiest way to test for exposure to MAI is by using a skin test similar to the PPD, but using antigens obtained from M. avium instead of M. tuberculosis.
The most common infection caused by MAI is in the lung with the formation of nodules and/or cavities. People with COPD or emphysema, especially if they are heavy drinkers of alcohol or cigarette smokers, are at risk. This population is over represented by white middle aged to elderly men. Infection in people with cystic fibrosis also occurs. The other main group that is affected by this organism is nonsmoking women over age 50. This is the most frequently encountered form of MAI infection in North America. In either situation, the infection may progress very slowly with minimal clinical evidence of infection or depending on host characteristics, such as the degree of immunosuppression, more rapid destruction of lung can occur. Therefore, the decision about whether or not to treat the infection must be based on many different criteria and not just whether or not the organism is growing in sputum or lung biopsy specimens. Involvement of infectious disease and pulmonary physicians is important to provide expert opinion concerning the need for therapy in any given situation.
An entity called “hot tub lung” is cause by an allergic reaction to MAI and this reflects exposure to the bacteria but not actual infection and growth of the bacteria in the lungs of the afflicted people.
In contrast, people with severe immunosuppression, such as advanced HIV infection (AIDS) is associated with disseminated MAI infection, with involvement of virtually any organ outside of the lungs. These patients typically have positive blood cultures are all of the signs and symptoms of advanced active infection.
Treatment of MAI infection usually involves the administration of at least 3 and up to 6 oral antibiotics for periods in excess of 6-12 months. As such, it is a major undertaking and institution of this therapy must be predicated on clear cut criteria for the need for treatment.
Now, reflecting on what you just read, despite the ubiquity of these organisms in our environment, I would venture to say that most of you have never seen anyone infected with these bacteria. Our immune systems, even when not 100% seem to be adequate in protecting us against these and other potential threats in our surroundings.
This entry was prompted by questions from one of our readers. If anyone has additional topics they would like addressed, please email me and I will see what I can do.
Posted by DrSugar on 09/11/2012 at 2:26 PM
|It's That Time Again
Well, it’s that time of the year again. Hard to believe. Influenza season, officially October 1 through May 31 is about to begin. That means it is time to get our influenza vaccine for the upcoming season. Fortunately, the vaccine shortages we experienced in the past are not an issue this year and many facilities already have initial stocks of the current vaccine.
As has been the case in the past, this year’s vaccine will contain 3 different virus: 1) an H1N1 strain related to the 2009 pandemic swine flu strain; 2) an H3N2 strain; and 3) an influenza B strain. The H1N1 strain was included in the vaccine last year and the year before. However, the other 2 strains are new for this year.
Several influenza related topics are worthy to consider at this point.
1) The push for universal vaccination for healthcare workers continues and, if not this year, certainly by next, most healthcare workers with direct patient contact will be required to receive influenza vaccine. Other than true allergy to the vaccine or its components, there simply is no excuse for healthcare workers to refuse the vaccine. As soon as you see notices that the vaccine is ready to be administered, walk (don’t run) to your nearest and most convenient location to receive your 2012-2013 influenza season influenza vaccine!
2) A new, variant H3N2 strain has appeared in swine and people who go to fairs and other venues where they can have up close contact with swine have been contracting this strain of influenza, even though it is formally not yet “flu season.” This strain, known as H3N2v is not reliably detected with our rapid flu tests. This variant strain contains the M gene (coding of the M antigen) from the H1N1 pandemic strain. This indicates that genetic material is being exchanged in the natural environment, even in the influenza “off-season.” Over 160 people have been infected with this strain of influenza and most have been under 18 years of age (indicating that older people may have some immunity secondary to exposure to related strains of the virus) and all have had contact with swine, indicating that person to person transmission is not very efficient in spreading the virus. However, if the “right” genes are acquired by this new strain of swine flu, that could change very quickly.
3) Avian flu is not off the radar map, either. Scientists have discovered that the H3N8 strain of avian flu has appeared in the seal population. Last autumn, 162 harbor seals washed up on the beaches of New Hampshire and Massachusetts and were found to be infected with the avian influenza strain H3N8. The most virulent avian flu strain to date has been H5N1, but this strain is not easily passed from person to person. Contact with infected birds is almost always needed to become infected with this strain. However, H5N1 influenza is highly lethal to humans, with mortality in excess of 50%. The importance of the H3N8 strain is that avian influenza viruses now appear to have made the jump to mammals and it likely can be spread among seal to seal. If the same happens with person to person transmission, we will have a real problem to deal with.
The good news is that our surveillance systems are the best they have been and the acceptance of the influenza vaccine is also at a very high level. Now all we need to do is to roll up our sleeves and get the shot.
Posted by DrSugar on 08/17/2012 at 10:39 AM
|The 5 (or is it 3?) Second Rule
I think that almost all of us have heard of, and probably employed at one time or another, the “5 second rule.” Simply stated, this rule dictates that if food falls on the floor or ground and you pick it up before 5 seconds have elapsed, then this food is safe to eat. This has recently made it into the news, with warnings from Jorge Parada, MD, the medical director of infection prevention and control at Loyola University Health System. Dr. Parada rightly points out that food coming into contact with where we stand will become contaminated immediately and the number of seconds that elapse before it is picked up certainly will have minimal effect on the degree of contamination. In addition, perfectly dry foods are likely to be less contaminated than those that are moist or wet. The longer an item remains on the floor will result in more bacteria (and presumably viruses and fungi) on that food than if it had been on the floor for a shorter period of time. However, if the few bacteria remaining on the food are highly pathogenic, you still could become ill following ingestion of these virulent bacteria. Obviously, the risk of getting infected increases with the number of bacteria present on the dropped food, and smaller numbers usually impart a smaller, but non-zero risk.
The flip side of this discussion is the observations that it is important for children to be exposed to microorganisms while they are young in order to decrease the risk of developing various allergies. This argues against obsessive use of hand sanitizers and environmental decontamination with disinfectants. A certain amount of comingling with our microscopic companions is really a good thing and appears to lead to the development of healthier children and adults.
Much of this discussion about dropping food on the floor is interesting, since I doubt there would be many takers, as Dr. Parada points out, if the food were dropped into a toilet. It seems like our perceptions of where the food lands are an important consideration, even if the toilet was freshly scrubbed and bleached and a heavily traveled floor hadn’t been washed in weeks.
So, have I ever employed the 5 second rule? Don’t ask!
Posted by DrSugar on 07/26/2012 at 12:10 PM
|Cats and Dogs
A new study just published in the journal Pediatrics draws attention to a possible benefit of growing up with pets . Finish researchers investigated the effect of contacts with dogs and cats in the first year of life. 397 children were followed from the time before they were born (while they were still incubating as fetuses) until beyond 1 year of age. Those children who had dogs at home had fewer respiratory tract illnesses and ear infections than children without such contact. They also required fewer antibiotics during that first year of life than those children raised in pet free households. The same effect was not observed with cats and this remains unexplained. Perhaps the differences in animal behavior are important, with dogs seemingly having more direct contact with their owners and members of the household than cats, which may be more aloof.
The authors provide an extensive discussion of the possible reasons for their observations, but no coherent explanation is evident. This study demonstrates the problems with descriptive epidemiological studies and assessing their implications for understanding the epidemiology and pathogenesis of disease.
As an interesting aside, only 4 of the 397 children were reported as being healthy for the entire year of observation. I wonder if that dismal statistic is unique to FInalnd or whether we might do better in sunny California.
If you are interested in reading the original article, you can find it here: http://pediatrics.aappublications.org/content/early/2012/07/03/peds.2011-2825.full.pdf+html
Posted by DrSugar on 07/10/2012 at 3:56 PM
|It's A Jungle Out There
At the 2012 annual meeting of the American Society for Microbiology, held in San Francisco this past weekened, researchers from the University of Houston have presented and interesting study. They studied the microbiology of the things normally found in hotel rooms. Samples were obtained from surfaces in hotel rooms in Texas, South Carolina, and Indiana. Not surprisingly, toilets and bathroom sinks were the most contaminated surfaces. However, high levels of bacteria were found on TV remote controls and bedside lamp switches. Housekeepers’ carts showed some f the highest levels of contamination, including sponges and mops. These latter fomites can possibly transfer bacteria from one room to another. The least amount of bacterial contamination was found on bed headboards, curtain rods and bathroom door handles (not sure which side of the door was sampled). The bacteria recovered and reported included coliforms, indicative of fecal contamination of the surfaces. You might recall that swimming areas are routinely closed when coliform counts reach a certain threshold.
Unfortunately, the study was small with only 3 rooms tested in each of the 3 states and only 19 surfaces in each room. The degree of bacterial contamination can be used as a rough guide to the level of overall cleanliness and there were no known cases of infections of the occupants of these rooms. This study provides additional rationale for good hand hygiene and frequent washing of hands or using hand sanitizer. It also is an indication that we also are probably relatively resistant to developing illness during our daily encounters with the bacterial world. Given that these rooms are cleaned by people with standard procedures for the cleaning of the rooms in a commercial environment, one wonders what a similar survey of our houses would uncover.
Posted by DrSugar on 06/19/2012 at 3:49 PM
CDC has recommended that people in the baby boomer generation, i.e. , those born 1945-1965, be tested for Hepatitis C Virus infection. This overall recommendation does not take into account other risk factors, such as intravenous drug use or other known potential exposures to the virus, such as tattoos, piercings, shared personal items like razors and tooth brushes, intranasal cocaine administration, and manicures. Since about 3% of the baby boomers are infected with HCV, we are talking about a large number of people who will be infected with this virus that causes chronic infections in about 80% of those who are exposed to the virus. Long term consequences of chronic infection include cirrhosis, liver failure and hepatocellular carcinoma.
Primary care providers or specialists in infectious disease and gastroenterology can order the appropriate testing. If a positive result is obtained, referral to a specialist in the management of HCV infection should be made.
More information is available at the CDC;s HCV website: http://www.cdc.gov/hepatitis/C/index.htm
Posted by DrSugar on 05/21/2012 at 11:00 AM
|For those of You with Trypanophobia*:
German researchers have reported that what you might feel during an injection is determined by your past experiences with injections along with information you get before the injection. In a cleverly done study, these investigators had volunteers watch videos that were positioned over one of the participant’s hands. The videos showed skin being pierced by a needle, swabbed by a Q tip or just a hand with nothing being done to it. At the same time they viewed the videos, the volunteers received electrical stimulation of their own hand. These electrical stimulations were either painful or non-painful. The participants then reported any sensations of pain and the degree of pain that they experienced.
The participants reported that they experienced pain and that the pain was more severe when they saw a needle pricking the hand compared to seeing the hand alone in the video. In addition, when the participants were told that the the needle or the Q tip would cause a painful, rather than a non-painful electrical stimulation, they reported higher pain levels than if they were told that the stimulation would not hurt. This demonstrated that the expectations prior to the activity (needle prick or Q tip swab) helped to determine the type of experience the volunteer had with that activity.
So, what is the lesson for those of us who administer injections or do procedures? It seems intuitive and now shown by experiment, that we should provide information to patients prior to any procedure to inculcate the expectation that the procedure or injection will not be that unpleasant. In addition, averting one’s eyes (when on the receiving end of an injection) will tend to minimize the discomfort when compared to watching the entire event.
Based on this study, I guess prior to administering an injection, the injector should not say to the injectee: “this will hurt you more than it will me.”
*fear of needles
Posted by DrSugar on 05/15/2012 at 12:44 PM
|Avian Influenza – Publication of New Research
You may have been following the saga of 2 research papers that had been accepted for publication, but whose contents were thought to be so sensitive in terms of being adaptable for nefarious means that publication of the papers has been delayed until the advisability of dissemination of the details of the research could be assessed. (How’s that for an opening sentence?) Various international groups met and discussed these papers and only one, the National Science Advisory Board for Biosecurity (NSABB), recommended that the methods section of the manuscripts be redacted so that potential terrorists could not use the information provided to create new strains of avian influenza and start a new and very lethal pandemic. An expert group convened by the World Health Organization came to the opposite conclusion. These papers are not yet published.
In a dramatic reversal and after new information about the research came to light, the NSABB changed its decision and is now recommending that both papers be published without any censoring of the contents of those papers. The viruses created by the researchers have been shown to be not as contagious as once thought and not as lethal as feared. While this instance of so called “dual use” research, that is, the results can be used for either good or bad purposes has apparently been resolved. We can expect this sort of research to continue and there are other viruses, such as Ebola virus and other viruses that cause a variety of different hemorrhagic fevers or the smallpox virus that could be used for terrorist purposes that are quite dangerous, especially if deliberately released into a non-immune population.
It is going to be important to continue to develop guidelines that will help direct future research and its publication. Should certain research be permitted at all or is some research simply too dangerous to allow in any place, at any time? If the research is done, are there circumstances that demand that specific details not be released when the research itself is published? We are just beginning to see the scientific and ethics communities dealing with these issues. It is interesting to me that the only group that recommended not publishing details of the influenza work was from the US. An international group did not think censorship was helpful or necessary.
A proactive approach to these issues will serve us much better than the retroactive steps taken in this particular instance. As citizens of the world who can be impacted by science, we need to make sure the conversation continues and that reasonable guidelines are promulgated that will have a beneficial effect on our lives. Policy based on fear alone is not likely to produce the best outcomes.
For those interested in additional reading, start with Science 335:1155-1156, 2012.
Posted by DrSugar on 04/04/2012 at 11:47 AM
|The Good News in Infectious Diseases
Many times in the world of Infectious Diseases (ID), we hear solely about the bad news that is out there in terms of infections, and there is tons of it, including progressive gram negative antibiotic resistanceon the local and national levels (i.e. superbugs like E coli or Klebsiella KPC’s), Clostidium difficile, flu outbreaks, etc. There is significant good news appearing in the world of ID as well. Examples of important infections where actual reductions in incidence are occurring include hospital-acquired MRSA and global tuberculosis. There are also significant advances in cutting edge technology available for rapid diagnosis of infections.
In terms of reduced incidence of important infections, consider the case of Hospital-Acquired MRSA, (HA-MRSA as opposed to Community-Acquired MRSA). Nationally, the fraction of Staph aureus isolates that are MRSA is about 58%, which is rising, but the absolute number of HA-MRSA infections leveled off in 2007 and then has declined since. Why? The change is generally credited to improved central line insertion practices and “bundles” as advocated by Peter Pronovost, M.D., from Johns Hopkins University School of Medicine. In fact, in a longitudinal study of Michigan ICU’s, the participants were able to eliminate central line-related infections using the bundle approach during the study period….completely! Other efforts nationally at preventing ventilator-associated pneumonia (VAP) have also played a role in HA-MRSA reduction.
On the global front, there is good news regarding tuberculosis. Although still a major threat to human health with 1.4 million TB deaths in 2010 (many in HIV+ persons) there was a reduction in global tuberculosis cases reported by WHO between 2006 and 2010. This was the first decline since records had been kept. In China, there was an 80% decline in TB mortality between 1990 and 2010. In the US, TB cases declined 3.8% between 2009 and 2010 to around 11,000 cases. This was the lowest prevalence since 1953 (MMWR).
At the same time some of our worst scourges are yielding, rapid molecular diagnostics of infectious diseases are now clinically available and can help dramatically reduce the time to detection of these and other infections. The traditional culture-based methods are gradually being replaced by faster technologies. Important examples of this include the TB Gene-Xpert system that SB County Public Health has recently purchased. This will virtually eliminate the 6 week waiting period for TB cultures on sputum samples. It is a PCR-based method that is sensitive for detection of TB DNA in AFB smear-negative and AFB smear-positive samples. In a recent clinical trial published in the New England Journal of Medicine, this technology was found to be >90% sensitive and >90% specific on respiratory samples. Rapid fluorescent hybridization techniques (FISH) are available and highly sensitive for detection of Candida in blood, with same-day results. This offers dramatically decreased door-to-antifungal time for some of our most critically ill patients, as is often the case in those with Candidemia (chemotherapy patients, post-op patients, TPN patients, dialysis patients, etc.) At Cottage Hospital, Clostridium difficile PCR is now in use, and data presented at the recent IDSA meeting by Lena Kang-Birken from the antibiotic stewardship team shows the time to diagnosis of patients at Cottage has dropped, as has the time patients spend in isolation awaiting test results. MRSA PCR’s are available that can be used on blood samples that accurately detect MRSA presence within hours of the blood being drawn. In the future, microarrays will give a complete picture of a person’s pathogen burden in a matter of minutes. Many of the organisms harming people are getting stronger but so are our tools for detecting them.
Posted by DrSugar on 03/08/2012 at 7:22 AM
|The Onion of Immunology
It seems like there is always something new to learn about our immune systems. You may be familiar with different kinds of lymphocytes: T cells, B cells, and natural killer cells. The B cells are the producers of antibodies and the T cells are the master controllers of the immune response. T cells are the ones targeted by HIV. New evidence about the function of B cells is very interesting.
Researchers at Harvard Medical School in Boston have discovered that B cells rendered incapable of producing antibodies produce a protein called type 1 interferon. It is well known that interferons display antiproliferative, antiviral and immunomodulatory effects. In experiments in mice, they found that mice with these handicapped B cells survived following infection with an otherwise lethal virus, “simply” by producing this protein and in the absence of an antibody response. These new observations provide evidence that in response to viral infections (this study) and bacterial infections (other recent studies), B cells can contribute to an effective host response to pathogens above and beyond producing antibodies. Interferon was one of the first cytokines discovered in the early 1950s and not only is it an important immune system signaling protein, it also has been synthesized in the laboratory in various forms as a “biologic” medication for the treatment of various conditions, for example, multiple sclerosis, hepatitis C and hepatitis B infections.
The immune response is rather like an onion, there are multiple layers underneath the ones we have already peeled off. It also is getting so complicated that it might make you want to cry.
Posted by DrSugar on 03/02/2012 at 11:32 AM
|Hepatitis C Virus
Hepatitis C is back in the news. A study published in the Annals of Internal Medicine indicates that deaths due to the Hepatitis C Virus have over taken deaths caused by HIV. Researchers looked at deaths from 1999 to 2007 and in 2007, HCV overtook HIV as a leading cause of death. Over 15,000 people in the US died in 2007 of complications related to HCV infection, whereas HIV related deaths decreased to 10,000 in that year. This has important implications, since end stage liver disease caused by cirrhosis and liver cancer are very expensive to treat and the ultimate outcome in most patients, with or without aggressive treatment is death. Moreover, there are important quality of life issues in patients with cirrhosis and end stage liver disease that need to be addressed on a case by case basis. A comprehensive plan to deliver compassionate end of life care in people with end stage liver disease is an important component of the management of people with HCV infection. Most practices that manage patients with HCV infection do not yet have such programs.
It is estimated that about 4 million people in the US are infected with HCV and 50-75% of these people have no idea that they are infected. These patients are a continued source of new infections, especially if they engage in intravenous drug use with sharing of needles and works. Identification of those who are infected with HCV will not only help to prevent spread of the virus, it will also allow timely therapy. You may remember that last year, 2 anti-HCV specific drugs were approved for treatment of the infection by FDA. Many more such compounds are under investigation. The HIV treatment and disease management paradigm is easily transferred to HCV disease management. As more patients with HCV are identified, it will be critical for the health care system to address their needs and ramp up resources to deal with each stage of this insidious infection.
For more details on HCV, see an earlier post on Nov 7, 2011 in this blog. The CDC website with information on HCV can be found at http://www.cdc.gov/hepatitis/c/.
Posted by DrSugar on 02/22/2012 at 4:50 PM
|Back in the News – Listeria Contamination of Food
Eggs from Michael Foods are being recalled from 34 states including California. The eggs, more than a million in number, have been hard-boiled and are sold in brine. The eggs may be contaminated with Listeria, which is an increasingly recognized bacteria that have been implicated in food borne outbreaks. The last time I wrote about this, we were talking about cantaloupes. As of now, no illnesses have been traced to this contamination. However, the incubation period can be long (up to about 2 months), so cases related to these eggs may still be reported.
Six brand names have been mentioned as involved in this recall: Columbia Valley Farms; GFS; Glenview Farms; Papetti's; Silverbrook; and Wholesome Farms. Only lot codes immediately preceded by a "1" and ending in a "W" are affected. The original FDA recall was initiated on January 26, but expanded on February 6, to include additional product, as a precautionary measure.
Listeria can cause a variety of symptoms including fever, muscle aches, diarrhea, headache (flu-like illness). Central nervous system infection, with encephalitis and meningitis can also occur. Everyone can be infected, but the most serious disease occurs in pregnant women, people with immunosuppression, and the elderly.
Once again, our food surveillance system seems to be working and these pre-emptive recalls are likely to become more frequent as contamination of our foods is increasingly recognized.
Posted by DrSugar on 02/06/2012 at 11:07 AM
|New Diagnostic Technique in TB
You may have heard about the dogs that can identify cancer in living people. Well, here is a new one.
Researchers at the Max Planck Institute for Infection Biology have reported on the ability of African giant pouched rats to identify the presence of Mycobacterium tuberculosis, the causative agent of TB, in infected sputum. These rats have been trained to identify volatile compounds produced by > tuberculosis and when presented with sputum from TB patients, those infected with non-tuberculous Mycobacteria (which also can cause lung disease) and sputum from uninfected people, these rats were quite adept at correctly identifying those patients who had tuberculosis.
Rats detected 45 of 56 confirmed cases of TB, 4 of 5 suspected cases of TB and 63 of 228 TB-negative subjects. This calculates to a sensitivity of 80%, specificity 72%, accuracy 74%, positive predictive value 42%, and negative predictive value of 94%. Simply put, if the rat ignored the sputum sample, they were correct 94% of the time in ruling out TB. Not bad for a rat.
In areas of the world where it is easier to train a rat to do this work than it is to buy expensive medical laboratory equipment, this method might have some applicability. Maybe there is also an opportunity for those who like to train animals to train an army of such rats to become involved in dealing with the increasing number of cases of tuberculosis that are being seen worldwide. Seriously, this low tech solution to a real problem may lead to additional research to identify volatile compounds that can be detected by sophisticated techniques such as mass spectrometry, since there is now evidence that there are specific volatile compounds in sputum from patients with tuberculosis. These should be able to be identified, isolated and further tested as markers for active TB.
If you are interested in what these rats look like, there are many pictures at this link:
Posted by DrSugar on 01/25/2012 at 10:20 AM
In the continuing evolution of bacteria in response to our antibiotics, investigators have identified a strain of Mycobacterium tuberculosis, the cause of TB, that is resistant to all known anti-TB drugs, in India. It is known as TDR for Totally Drug Resistant tuberculosis. This is not a new development, since TDR TB organisms have been found in Italy in 2007 and in Iran in 2009, but it does make one pay attention to this ominous situation.
TDR tuberculosis is the natural progression from Multi-Drug Resistant (MDR) and Extensively Drug Resistant (XDR) tuberculosis. The World Health Organization says that XDR-TB is present in at least in 58 countries, with an estimated 25,000 cases occurring each year. It is critical to identify people who are infected with these drug resistant bacteria, since they are contagious and can spread the infection to many other people if diagnosis is delayed. In addition, having these infected people take the usual anti-TB drugs is useless, as they will not work in this clinical situation. Specific combinations of second and third line drugs, often with significant toxicities (which is one reason they are not used as first line therapy) must be used, requiring participation of specialists familiar with the treatment of these hard to treat infections.
Possibly because tuberculosis has been a problem primarily in the developing world, where expensive drugs are not affordable, there has been relatively little research being done to identify new anti-TB drugs. There have been no new first line drugs introduced for the treatment of TB for over 50 years. However, one of the later generation fluoroquinolones, moxifloxacin, has been identified as a potent and very useful agent for the use in people infected with tuberculosis susceptible to the drug. This is both good news and bad news. The bad news is the use of moxifloxacin (and other fluoroquinolones) in many patients with pneumonia of unknown cause. If the person actually has tuberculosis and not the garden variety of community acquired pneumonia, then they are effectively being treated with only one drug for tuberculosis. Single drug therapy for tuberculosis is guaranteed to result in the development of resistance. Moreover, for a short period of time, the person with tuberculosis and not just simple bacterial pneumonia may clinically improve, since the fluoroquinolones (including levofloxacin) are so active against the organisms. However, once resistance develops the pneumonia and symptoms return and the disease marches on until a correct diagnosis is made. When cough and other symptoms worsen, the ill person’s contacts are exposed to the new mutant bacteria, now resistant to the antibiotic and the disease now spreads well beyond the initial index case.
In this era of easy global travel, what happens on the other side of the world today, can easily happen in our area tomorrow. This is no time to be complacent.
Posted by DrSugar on 01/17/2012 at 3:38 PM
|Avian Influenza in the Laboratory
So, here is an issue to contemplate as we start the new year. Scientists have modified the avian influenza virus (H5N1) so that it is more infectious to humans. You might remember from earlier discussions that avian influenza is not very easily spread from person to person, but it is a very bad infection to acquire, with a mortality rate of about 60%. The virus modified in the laboratory can now infect people directly and would be expected to be highly contagious, with a much greater risk of person to person spread. In response to the pending publication of this information, the National Institutes of Health (NIH) has requested that certain details, such as how the scientists actually made the critical modifications to the virus to make it contagious to humans, be redacted from any publications of this work. The World Health Organization has also expressed concern that if the information fell into the wrong hands, a very dangerous biological weapon could be constructed. The research was supported by grants from the federal government.
There are several issues here. Is censorship of critical details of the methods used by these researchers an effective way to prevent biological terrorism? Would terrorists be able to capitalize on the information to create an effective biological weapon? What role do scientists have in responsibly reporting the fruits of their research? Should this research even have been done? It is very important that we, as a society, address these concerns and come to some mutually agreeable solutions so that there are some guidelines under which research can be ethically and responsibly reported.
Posted by DrSugar on 01/04/2012 at 10:20 AM
Have you ever had the experience of being bitten by mosquitoes, or not, and everyone around you had the opposite experience? Some people are like mosquito magnets and will be bitten preferentially, when others in the same area are minimally affected. Why does that happen?
It has been known for some time that bacteria are important in the production of body odor. Without bacteria, human sweat has no odor. Skin bacteria convert non-volatile chemicals in sweat into volatile compounds that have characteristic smells. Moreover, specific bacteria result in specific smells.
Researchers at Wageningen University in the Netherlands carried out experiments with the mosquito that transmits malaria, the Anopheles mosquito. They found that people with a higher number, but lower diversity of bacteria on their skin were more apt to attract the Anopheles mosquito to their skin and therefore, were more likely to be bitten. The researchers think that people with a more diverse number of bacteria on their skin may be relatively protected from attracting the mosquitoes because the bacteria make compounds that interfere with the normal attraction of the mosquitoes. In addition, the data revealed that certain bacteria were associated with relative protection from attracting Anopheles. The authors speculated that identification of the volatile chemicals produced by some of the bacteria that seemed to not attract the mosquitoes might lead to the development of new mosquito repellents.
Whether this same mechanism holds for other mosquitoes remains to be seen. This is just another example of our symbiotic relationship with bacteria. You can't live without 'em.
Posted by DrSugar on 12/29/2011 at 3:04 PM
All of the members of the Department of Infectious Diseases at Sansum Clinic extend our wishes to our readers for a happy, healthy, and restful holiday season and a very Happy New Year!
Posted by DrSugar on 12/23/2011 at 10:18 AM
|Chronic Fatigue Syndrome
Chronic fatigue syndrome (CFS) is an enigmatic illness characterized by profound fatigue, body pain, and a variety of other symptoms. The cause is unknown. However, in an apparent breakthrough published in Science in 2009, a viral cause of the illness was proposed. This meant that there could be work done on finding appropriate specific treatments for the disease. However, work to confirm the linkage of the virus, xenotropic murine leukemia virus–related virus (XMRV), indicated that this was not a true finding. In fact, the samples used in the original study were found to be contaminated by this virus, rendering the results meaningless. Science has now retracted the original article. Thus, the cause of CFS remains unknown.
There are several conditions that have symptoms similar to CFS, all of which have no plausible etiology yet discovered and which cause serious negative impact on people’s lives. We will have more to say about CFS and the related conditions in the future.
Posted by DrSugar on 12/23/2011 at 10:17 AM
|Influenza - The Virus Is Still Alive
We are well into the influenza season and the news has been relatively quiet so far. Only sporadic cases have been recorded in California and most of the western US. Vaccine utilization rates across health care facilities is up and that is a good sign that people are getting the message that influenza vaccine is safe and effective. For healthcare workers, it also means that we personally will not pose a risk to our patients by infecting them as we are incubating an active case of influenza. The trend toward mandatory influenza vaccine administration for healthcare workers has picked up steam and is being actively considered by many hospitals. This policy has already been implemented in some medical centers across the country. I expect that many more institutions will adapt this approach for the next influenza season.
Our national surveillance system has been doing a great job of identifying influenza cases, noting the beginning of increased activity of the disease and the identification of new mutants of the virus. There are some interesting developments along these lines. A Minnesota infant has been tested positive for H1N2, a strain of influenza that is common in pigs in the Upper Midwest. This baby and his family did not have any contact with swine, so this represents a random mutation of existing viruses to display these antigens. Fortunately, the boy recovered, indicating that this virus did not become more virulent than the seasonal strains that we have to contend with .
Additional mutant strains have been identified. One child in West Virginia was infected with a novel H3N2 virus that had genes from swine, birds, and human influenza viruses. The M antigen was derived from the 2009 H1N1 pandemic strain. There have been 10 prior infections with this specific virus spread across 4 other states: Indiana (2), Pennsylvania (3), Maine (2), and Iowa (3). These viruses are very different than the H3N2 viruses that are circulating this flu season but are distantly related to the H3N2 viruses that circulated among the human population n the 1990s. Therefore, some adults may have residual immunity to these mutant viruses, a concept supported by the observation that 10 or the 11 cases of infection with this virus have been in children
Avian influenza continues to infect birds in various locations around the globe and occasional human cases continue to be reported. This virus is not particularly contagious from a person to person perspective, but mortality continues to be around 60%. If this virus ever figures out how to infect humans more easily, we could be in for another pandemic situation.
In the meantime, make sure you have had your seasonal flu vaccine.
Posted by DrSugar on 12/14/2011 at 11:27 AM
Almost all of us have experienced the tuberculin skin test, also known as a PPD (purified protein derivative). This skin test has been the cornerstone of diagnosing exposure to tuberculosis for decades. When positive, we can be reasonably confident that the person has been exposed to Mycobacterium tuberculosis, the bacteria that causes TB, and that the tuberculosis bacteria are in the lungs of the skin test positive person.
Once inhaled, the M. tuberculosis remains in the lungs, usually contained by the person’s immune system. However, over the course of one’s lifetime, there is an approximate 15% chance of the bacteria overcoming this immune response and causing active tuberculosis. This usually is in the form of pulmonary tuberculosis, which can cause fevers, night sweats, weight loss, cough, production of sputum, hemoptysis (coughing up blood). Rarely, the bacteria can disseminate from the lungs and involve most any organ in the body. If a person needs an organ transplant or requires immunosuppressive therapy, these latent bacteria can start to grow and cause serious illness in the otherwise asymptomatic person with a positive PPD. When in the latent phase, the person is not contagious to any of his contacts. It is only when the bacteria start to grow and cause actual active infection and illness that the person becomes infectious to those around him.
Fortunately, if we can identify those who have been exposed, early enough, we can prescribe therapy to prevent the activation of active tuberculosis. The traditional therapy has been 9 months of daily isoniazid therapy taken daily (a total of 270 doses). This reduces the risk of activation of the bacteria within the lungs to close to 0. A new regimen has now received approval. This new approach consists of INH and rifapentine (an antibiotic active against M. tuberculosis), each given one day a week for only 12 weeks – a total of 12 doses in all! It is recommended that the 2 drugs be administered by health professionals, so that the patient can be observed taking the required pills, in other words, DOT, directly observed therapy. Missing even one dose of this weekly therapy may seriously degrade its ability to protect people from reactivating the latent bacteria in their lungs. This new regimen, in addition to being as effective as 9 months of INH alone, appears to have less toxicity, especially with respect to hepatitis, the most serious complication of taking INH.
We will be instituting this new regimen in those people with positive PPDs, who are eligible to take this shortened course of therapy for latent tuberculosis.
In a future entry, I will discuss the new blood tests for diagnosing tuberculosis exposure and how these should be used vis-à-vis the PPD.
Posted by DrSugar on 12/09/2011 at 11:15 AM
|World AIDS Day - December 1, 2011
Today, December 1, 2011, is World AIDS Day. This day was organized to draw attention to HIV infection and AIDS and to have us reflect where we have been and where we are headed. The theme for this years World AIDS Day is Getting to Zero: Zero new HIV infections, Zero discrimination, Zero AIDS-related deaths. Great strides in the understanding of the pathogenesis, pathophysiology, and treatment have been made. However, there still is no cure and virtually all people who become infected will require life long anti-retroviral therapy. This therapy has been extraordinarily effective in prolonging life, to the extent that diseases of older age are becoming more important in the day to day existence of HIV infected people.
The not so encouraging news about HIV is that many people who are at greatest risk (those who do not practice safer sex or who use injectable drugs) have become complacent about the possibility of becoming infected and they point to the efficacy of drug therapy to bail them out if they do become infected. While very effective at controlling the virus, these drugs are costly and have significant side effects. Prevention of infection clearly is the goal, until such time that an effective vaccine becomes available.
Today we can stop to consider how far the science has progressed in the 30 years since the illness was first described (1981) and the 28 years since the virus was discovered (1983). There is much more to learn about this infection and the disease that it causes. In the meantime, we are fortunate in being able to treat those who need it, with life saving medications. Getting to Zero is a laudable goal and one that will take additional hard work to achieve.
For more information on World AIDS Day, see http://aids.gov/world-aids-day/
Posted by DrSugar on 12/01/2011 at 10:39 AM
|More On Hepatitis Viruses- New Kid on the Block
We have all heard of various hepatitis viruses: A, B, C (formerly known as non-A non-B; see earlier blog entry) hepatitis. Hepatitis A is often spread through fecal-oral contamination of foods and water and other items. Both Hepatitis B and C viruses are transmitted by the blood borne route. Vaccines for Hepatitis A and B are available and are extremely effective and safe. I have written previously about hepatitis C. I would now like to introduce a “new” virus to add to our vocabulary.
Hepatitis E virus was first described in 1955 in New Delhi, India. It presents with a similar mode of transmission as Hepatitis A, with fecally contaminated water the most common vehicle. Unlike Hepatitis A Virus, however, blood borne transmission of Hepatitis E Virus has been described. The reason to bring this up today is that Hepatitis E virus has now been found for the first time in farmed rabbits living in the US. This virus was found in rabbits in China in 2009, in pigs in 1997 and in many other animals species, thereafter, including, deer, wild boar, and rats, Interestingly, Hepatitis E Virus in both pigs and rabbits can be transmitted to people.
Hepatitis E infection in pregnant woman is a very serious illness and fatal infections in pregnant women are not uncommon. Otherwise it is similar to hepatitis A, in that there is no chronic carrier infection established after the acute infection resolves. The acute infection can be more severe though than that seen in Hepatitis A Virus infection. In the US, patients with Hepatitis E have usually been out of the country, visiting or living in endemic regions (Asia, Africa, the Middle East, and Central America). When traveling to these areas, it is particularly important to do as much as you can to avoid exposure to this and other viruses and pathogenic bacteria, such as avoiding drinking water of unknown purity, and uncooked fruits or vegetables or shell fish.
In case you were wondering, there is a hepatitis D virus. It actually is called hepatitis delta virus and it is a defective virus in that it can only grow in the presence of active infection with the hepatitis B virus. If Hepatitis B Virus is not present, neither is the delta virus.
Posted by DrSugar on 11/29/2011 at 11:01 AM
|Say It Ain't So.....
Aided by social networking and the internet, a group of parents is sending lollipops licked by their children, who have active chickenpox, to parents who wish that their healthy children develop chickenpox, in a 21st century version of the chickenpox party. Years ago, parents hoping to have their children get chickenpox before they got too old and therefore would be subject to more severe infection, would have healthy kids from the neighborhood come to play with the chickenpox infected child. Since chickenpox is very contagious, these healthy children would often develop varicella and henceforth be immune to the disease. However, there now exists a much safer alternative in the form of a vaccine to prevent chickenpox (varicella). Chickenpox parties should have gone the route of blood letting and alchemy.
Perhaps working from this experience, parents wanting their children to get chickenpox are now obtaining partially eaten lollipops used by chickenpox infected children to feed to their own healthy children, In some perverted sense of logic, if one can call it that, the parents think that sucking on a lollipop used by a chickenpox infected child is safer than having their child immunized. This is wrong on so many levels it is hard to know where to begin. The most obvious is that these lollipops might be transmitting other infections and pathogens such as MRSA, possibly blood borne pathogens like Hepatitis B Virus, Hepatitis C Virus, and HIV, Herpes simplex virus, EBV, CMV, and many others. In addition, mailing infected lollipops is illegal.
While this misguided effort apparently has its roots in Tennessee, it is a multi-state affair. It points out that there is still much work to be done to show parents that modern vaccines are safe, effective, and have an important place in preventing infections that can be serious and life threatening. Just because it is “all natural” does not mean it is safe. That people could think that eating virus contaminated food (for which there is no quality control) obtained from strangers through internet sites is almost beyond comprehension. That they think that this is safer than using readily available vaccines is insane.
Posted by DrSugar on 11/22/2011 at 7:30 AM
|Antibiotic Awareness Week
November 14-20, 2011 has been Antibiotic Awareness Week. Started in 2008, the goal of this project is to draw attention to the use and misuse of antibiotics and to encourage providers to prescribe antibiotics thoughtfully and to educate everyone that there is a right way and a wrong way to prescribe antibiotics. It was initiated by the CDC (Centers for Disease Control, based in Atlanta, Georgia) and it attempts to coordinate the efforts of CDC’s Get Smart: Know When Antibiotics Work campaign with other state and local groups that educate interested parties about the proper use of antibiotics. More details can be found on the CDC’s website: http://www.cdc.gov/getsmart/campaign-materials/week/overview.html. The importance of appropriate antibiotic use and the rapid development of bacterial resistance to available antibiotics also have been highlighted over the past several years. This Friday, November 18, is also the 4th annual European Antibiotic Awareness Day, indicating that efforts to encourage good antibiotic prescribing habits have taken on an international flavor. For more information on the European program, see http://ecdc.europa.eu/en/EAAD/Pages/Home.aspx/.
Securing a better handle on the development of antibiotic resistance will take a combined effort of physicians and other healthcare providers who write prescriptions for antibiotics, the agricultural industry that uses antibiotics as growth factors in the animals they raise for meat, veterinarians who prescribe antibiotics for animals, and the general population, who need to understand what antibiotics should be used for and when they are inappropriate to take. A more informed patient population will go a long way to relieving pressure on healthcare providers to write prescriptions for antibiotics.
We should also use the events of this week to empty our medicine cabinets of old prescriptions that have not been completely taken. Not having extra antibiotics in our houses may help control the urge to take antibiotics just because they are within reach. Each of us has an increasingly important responsibility to help conserve the activity of the antibiotics we have available.
If you have questions or concerns about local issues with respect to antibiotic resistance, enlist the help of our Santa Barbara infectious disease physicians. Education is part of what we do.
Posted by DrSugar on 11/17/2011 at 8:09 AM
|The Silent Epidemic
Over 170 million people in the world and about 4 million in the United States are infected with the Hepatitis C Virus. For years, the medical community was familiar with non-A non-B hepatitis, but it was only in the late 1980s that the virus responsible for this chronic infection was identified. Experimental models of infection with this virus have only recently been described, so many aspects of the biology and pathogenesis of the disease it causes are still beginning to be elucidated. Its importance as a cause of morbidity and mortality is increasing as we continue to identify people who are chronically infected.
The Hepatitis C Virus (HCV) is in the family Flaviviridae. As such, its closest relatives are the Yellow Fever Virus and Dengue Virus, 2 viruses that are transmitted in different ways and cause different diseases than HCV. The virus is transmitted through blood and bodily secretions that might contain blood. Until a blood test to identify infected people was developed in the early 1990s, blood transfusion was the major risk factor for transmission of the virus. Intravenous drug users are the major population who continue to transmit the infection. Sexual transmission is also a risk factor, but much less than that posed by blood to blood exchange. Both HIV and Hepatitis B Virus are much more readily transmitted sexually than is HCV. Evidence for the presence of HCV can also be found in saliva, tears, seminal fluid, ascitic fluid, and cerebrospinal fluid.
In the US, there are 4 major genotypes causing infection, 1,2,3, and 4. Types 1 and 2 are the most commonly found. The genotype will predict how likely it is that therapy will successfully eradicate the virus.
Because of the route of transmission, people who are infected with HCV should also be tested for Hepatitis B and HIV.
Approximately 80% of people infected with HCV become chronically infected. Thus, 20% can clear the virus after exposure and are identified by having only HCV antibody detected when that blood test is performed. Those chronically infected will have varying amounts of viral particles circulating in the blood and measurement of the amount of virus in the blood is routinely done and is known as the “viral load.” Viral loads of several hundred to several million can be seen, but the degree of illness is not related to the absolute number of virus detected in the blood.
Acute HCV infection can be asymptomatic, but can present as does any viral hepatitis: malaise, fever, right upper quadrant pain, jaundice, and loss of appetite. The incubation period (time from exposure to onset of symptoms) is about 7 weeks. If people infected with the HCV can be identified at this stage, early treatment might help to prevent the development of chronic infection. Measuring HCV viral load and HCV antibody production in people with acute hepatitis will help to identify those in need of further evaluation and possible treatment.
In the 80% of people who develop chronic infection, there is little clinical evidence of infection. While many patients may be fatigued or have depression, it is not clear that these symptoms are related to the infection. Selective liver function tests (transaminases) may fluctuate from normal to elevated over the years, and decades may pass before the infection causes any identifiable abnormalities. Chronic infection can lead to the development of cirrhosis in about 25% of people and in those who develop cirrhosis, liver cancer may develop in 20% of those patients. Within 5 years of the development of cirrhosis, 10-20% of HCV infected patients will decompensate with all of the manifestations of end stage liver disease appearing over the span of weeks to months. Patients infected with HCV who have cirrhosis should be seen by a specialist at least every 6 months for proper follow up evaluations.
Liver damage caused by HCV is a result of the body, in an attempt to kill the virus, damaging the cells where the virus lives, that is, the liver cells themselves. The body’s immune system does not specifically target the virus for destruction. As a result of the chronic inflammation, scarring of the liver occurs and when it involves a critical mass of the liver, the scarring is known as cirrhosis.
The goals of treatment are to arrest the damage being caused to the liver and to eradicate the virus from the liver cells.
A major advance in the management of HCV infected individuals came with the recognition that interferon injections and oral ribavirin tablets could lead to response in some infected patients. Patients infected with genotypes 1 and 4 require 48 weeks of therapy and sometimes longer, whereas “just” 24 weeks of therapy are used for genotypes 2 and 3.
Just this past summer, 2 new drugs, which specifically target the HCV virus, were approved by the FDA. These drugs are called telaprevir and boceprevir. Using just interferon and ribavirin, response rates are about 40-50% in genotype 1 infected patients and 80-90% in genotype 2 infected patients. When either one of the new drugs are used in combination with interferon and ribavirin in the treratment of people with genotype 1 infection, approximately 80% of patients clear the virus in about 24 weeks (as opposed to at least 48 weeks with interferon and ribavirin alone) of therapy, although longer durations may be needed in some patients. These new drugs are not currently approved for use in non-genotype 1 infections.
There are newer drugs in the pipeline that offer the promise of an entirely oral regimen, bypassing at least the interferon injections.
This brief overview of Hepatitis C Virus should make us all aware of this cause of a true “silent epidemic” and to test our patients who might have had risk factors as “far back” as the 1960s and 1970s. We can anticipate seeing many people with end stage liver disease and all of its manifestations over, at least, the next decade. Continued rational strategies to minimize risk of transmission to the IV drug using public (like needle exchange programs) need to be part of our approach to this preventable disease. An important first step, however, is to identify those who are already infected and who can transmit the infection to others.
Posted by DrSugar on 11/07/2011 at 2:49 PM
|Rabies Alert - Infected Cat
The presence of rabies in skunks and bats in Santa Barbara County is well known. For the first time in 30 years, rabies has been found in a cat. The cat in question was found in Hope Ranch in the 400 block of Las Palmas Drive. It is not known if the cat was domestic or feral, but it tested positive for the rabies virus. The few people who were exposed to the cat are being given rabies vaccine. The Public Health Department has put out a press release indicating that the cat was a shorthair black female about 1 year old. The owner of the cat is unknown and efforts have been made to determine who the owner is, since there may have been an exposure that requires rabies vaccine.
Rabies is transmitted by saliva, and bites and scratches from an infected animal can infect other animals, including humans. It is critical to start post exposure prophylaxis with the rabies vaccine in order to abort an infection. Clinically evident rabies is almost universally fatal.
If animals around you are noted to be behaving strangely, stay away and call Animal Services at 805-681-5285. If you have had an exposure to the cat being discussed above or to other rabid animals, call Disease Control at 805-681-5280. We can attempt to answer general questions on this blog or through emails or phone calls to us.
Posted by DrSugar on 11/01/2011 at 5:00 PM
|Food Borne Outbreak - Redux
The CDC has updated the cantloupe associated listeriosis outbreak. There have been 133 people infected from 26 states. Twenty-eight people have died and one pregnant woman had a miscarriage. Since the incubation period for listeriosis can be up to 70 days, more cases can be expected. Moreover, the bacteria can grow well at room temperature and at temperatures found in most refrigerators. The only cantaloupes known to be responsible for this large food borne outbreak have been grown in the Rocky Ford area of Colorado. Unsanitary conditions were found at the farm, leading to contamination of the fruit.
In a related “don’t eat this contaminated food” focus, Turksih pine nuts have been found to be contaminated with Salmonella enteritidis in New York State. The pine nuts of interest were found in bulk bins at Wegmans grocery stores. So far, 42 people became ill and 2 have been hospitalized. There have been no deaths due to this infection yet. Illnesses began after August 20, 2011 and cases from 6 states have been reported (Arizona (1), Maryland (1), New Jersey (2), New York (26), Pennsylvania (8), and Virginia (4).
The pine nuts in question are being recalled by the grocery store and the investigation into this outbreak is continuing. The true extent of this outbreak will not be known until further details are uncovered.
It seems like there are more episodes of contaminated food supply being reported. This undoubtedly is due to a major enhancement of our surveillance system and better reporting and recording of such events. Many aspects of our national security system have been enhanced since the attacks of Sept 11, 2001. The apparent increase in reports of food borne outbreaks are a direct result of the improvement in surveillance and communication between health departments, healthcare providers, and the many agencies responsible for the oversight of our food supply. The increase in these reports is a direct indication that the system is working. Next step: improving the quality of the food supply so that there is no need to report on such episodes.
Posted by DrSugar on 10/27/2011 at 4:20 PM
My intent in writing this blog is not to scare the reader, but to present topical interesting infectious disease information. However, in my daily reading, I find that we are being constantly informed of dangers that lurk in the world around us. In that vein, here is yet another study.
Investigators from Kimberly-Clark Professional, a unit of personal hygiene company Kimberly-Clark Corp, have cultured familiar objects that we use on a regular basis. The researchers went to 6 cities (Atlanta, Chicago, Dallas, Los Angeles, Miami and Philadelphia) and started culturing stuff. Here is what they found. The top contaminated objects (evidence was obtained for the presence of bacteria and viruses) were gas pump handles, followed by handles on public mailboxes, escalator rails and ATM buttons.
OK, I think we are getting the point. We live in a world that we share with bacteria and other microorganisms. In order to protect ourselves from becoming ill from the pathogenic members of these invisible germs, we need to make hand washing and use of hand sanitizer a regular part of our hygiene when touching fomites in public places. I don’t think we need to become obsessed about this, but a certain degree of respect for what is in our environment will likely go a long way to minimizing our risk of developing colds, boils, and other infectious diseases. A corollary of this is the importance of a solid science education presented in our schools. Our appreciation of the germ theory needs to start at an early age.
One last thing. Did you get your influenza vaccine yet?
Posted by DrSugar on 10/25/2011 at 10:47 AM
The reasons to keep ourselves immunized against otherwise preventable diseases continue to mount. UC Berkeley has announced the identification of cases of mumps amongst its student population. Typically, people receive the MMR vaccine (measles, mumps, rubella) at age 12-15 moths and then about 4 weeks later. Because of fears of autism (which have been thoroughly debunked, as pointed out in an earlier blog entry), many people did not receive the MMR vaccine and therefore are at some risk of developing one or more of these diseases. Measles has been a problem over the past year in many localities and now mumps is occurring, pointing out that either the MMR vaccine was not given or immunity to the vaccine given in early childhood has begun to wane.
In the non-epidemic situation, if a person, aged 19-49, does not have documentation that they have had the MMR series of 2 injections, they should get one or 2 injections . Certain individuals age 50 and older might be candidates for MMR “booster” if they have specific risk factors that might expose them to these viruses. In the epidemic situation with any of these 3 infections, administration of a third injection of the vaccine might have a role in stopping the spread of the virus causing the outbreak.
More details are to be expected from the UC Berkeley experience. However, it is clear that without antibodies to these and other pathogens, people will continue to fall ill with these preventable diseases. We need to take a 21st century approach to infection prevention.
Posted by DrSugar on 10/21/2011 at 11:38 AM
|Global Handwashing Day
I must admit that I missed the occasion on October 15: Global Handwashing Day. In honor of this occasion, researchers at the London School of Hygiene & Tropical Medicine and Queen Mary, University of London have reported that many cell phones are contaminated with E. coli, a marker for fecal contamination. The researchers went to 12 cities and collected 390 samples from cellphones and hands of the research subjects. 95% of the subjects said that they washed their hands with soap and water after going to the bathroom. However, 92% of the cell phones that were cultured and 82% of the hands of the same subjects had bacteria on them. Of particular note, 16% of hands and 16% of the cellphones were culture positive for E. coli. The implications for the spread of bacteria are clear.
So, either many of the subjects did not wash their hands as they claimed, or we will need to refer most , if not all, adults to specific instructions on the best way to wash their hands. This entails adequately soaping up, enough time (try singing Happy Birthday without rushing it, all the way through), with attention paid to getting the soap between fingers and under nails and then vigorously rinsing under a steady stream of water. Use a paper towel to turn off the faucet, since presumably you turned it on with contaminated hands to begin this exercise.
Once again, attention to detail when washing our hands may go a long way in helping to limit the spread of infectious microorganisms.
The list of everyday objects that may carry pathogens continues to grow: neckties, white coats, hands, countertops, keyboards. The list goes on and on. We live in a bacterial world. Be safe out there!
Posted by DrSugar on 10/17/2011 at 1:17 PM
|Blog Post Notifications
We are working on trying to obtain a notificaiton system so that you will know of new entries to our blog. Since we do not have a mechanism yet, there are 2 options: 1) check this website yourself, once or twice every week to see what is there or 2) send me you email address and I will send emails to those I have on a master list each time a new blog entry or comment is posted. My email address is email@example.com
Posted by DrSugar on 10/13/2011 at 10:29 AM
|Influenza Vaccine Time
It’s influenza vaccine time again. This year’s vaccine, as we discussed previously, contains the same 3 viruses as last year. The one thing that is different now is that additional research has shown that vaccines continue to be safe for the overwhelming majority of people who take them and they unequivocally prevent diseases that can be fatal. The best example of this is the revelation that the purported link between measles, mumps, and rubella vaccine (MMR) and autism was totally fabricated. The paper describing this “link” was retracted and the entire episode has been described as an “elaborate fraud.” The fear of serious reactions to vaccines, especially those given to our children has had a marked effect on the acceptance of all vaccines and has made it difficult in some circumstances for healthcare providers to successfully immunize their patients.
With respect to the importance of keeping ourselves immunized against infections that can be serious to our health, CDC has recently noted that last influenza season, 115 children (under 18 years old) died of influenza related complications. Nearly half of the deaths were in previously healthy children with no underlying medical illnesses. Most of the children were younger than 2 years old. As we learned from the 2009 pandemic, young children are at increased risk for serious complications if they develop influenza. 77% of the kids who died from influenza were eligible for the flu vaccine, but never received it. CDC recommends that all children over 6 months of age be vaccinated against influenza. We have plenty of vaccine this year and the vaccinations have begun. Don’t reject the vaccine because of irrational fears or concerns about the vaccine’s safety.
The most common side effects from the influenza vaccine are sore arm (where the injection was given), headache, low grade fever, chills, and muscle aches. These symptoms can last 1-2 days after the injection and then resolve. These symptoms do not mean you got the flu from the shot. This indicates that your body is responding to the components of the vaccine. These symptoms are not serious and not a cause for alarm. They can be easily controlled with some ibuprofen or acetaminophen. Very rarely more serious complications can occur and include Guillain Barre syndrome, a neurological condition characterized by ascending weakness and possibly paralysis, This was first seen with the swine flu vaccine in 1976, but not with every lot of influenza vaccine from year to year. It is a very rare complication when it does occur. A study published in the British Medical Journal on July 12, 2011, concluded that the 2009 pandemic influenza vaccine was not associated with the development of Guillain Barre syndrome. However, given the power of the study to detect this rare complication. statistical analysis could not rule out the development of up to 3 excess cases of Guillain Barre syndrome per million people who received the vaccine. This number represents statistical probability of excess cases developing, the actual number observed was not different than what would be expected in the general population who did not receive the vaccine.
All in all, the influenza vaccine is well tolerated and is safe. It is important to roll up your sleeves and be immunized against influenza. The data support this decision and our collective health depends on wise action on our part.
Posted by DrSugar on 10/13/2011 at 10:28 AM
|Welcome to Our Blog
This will be the first of, hopefully, many communications between the Department of Infectious Diseases at Sansum Clinic and the medical community practicing at Sansum Clinic and the Cottage Hospitals. Since these communications will be posted as a blog on the internet, it is expected that interested non-medical people will be reading our content from time to time. We want to be able to communicate interesting infectious disease information, as well as timely commentary on important infectious disease issues that impact our community.
Our inaugural post can be found just below this paragraph.
Alan M. Sugar, M.D.
David T. Fisk, M.D.
Mary-Lousie Scully, M.D.
Posted by DrSugar on 10/06/2011 at 11:09 AM
Influenza continues to occupy our attention at the beginning of the 2011-2012 flu season. While we are awaiting the appearance of our first influenza cases, there has been continued activity across the globe. As I mentioned in a previous post, avian influenza has been smoldering in the East. Now authorities in India have reported a mutant H5N1 strain of influenza has infected chickens in West Bengal. Avian influenza has been contagious for poultry and other birds but rather difficult to transmit from person to person. Given that the human case fatality rate is well over 50%, it is a good thing that the virus is not easier spread amongst humans. Officials in West Bengal have begun culling chickens and destroying eggs in an attempt to abort the continued activity. Avian flu continues to infect birds in Viet Nam and China.
Now for a little biology.
There are 3 types of influenza viruses: A, B, and C. Epidemics are caused by types A and B. Type C viruses usually cause mild respiratory tract infections and not epidemics. Type A influenza viruses are divided into subtypes based on 2 of the surface proteins: the hemaglutinin (H) and neuraminidase (N). There are 16 H subtypes and 9 different N subtypes and the viruses found circulating during the flu season can be described by this system. So, H1N1, indicates subtype 1 H and subtype 1 N proteins whereas H3N2 depicts the subtype 3 H and subtype 2 N protein.
Type A viruses are the ones we worry about the most each year.
Types B and C viruses are not further subtyped.
The 2009 pandemic made popular the designation of influenza viruses, e.g., H1N1, H3N2. The “H” stands for the hemagglutinin and the “N”, neuraminidase, 2 molecules on the surface of the virus that easily mutate and therefore, are responsible for our need for annual immunization for influenza. Major changes in these are called “antigenic shift”, and minor changes are called antigenic drifts. Epidemics and pandemics are caused by viruses that have undergone the major change, the antigenic shift, while, more minor changes in these proteins, i.e., antigenic drift is responsible for more localized outbreaks. The ability of influenza viruses to infect various species of animals, including humans, depends on the specific H and N proteins present on the virus surface. Most bird influenza viruses (avian flu) prefer to infect only birds and find it very difficult to bind to the human respiratory tract, making this virus relatively hard for humans to contract. The one animal though that is a host for both bird and human influenza viruses is the pig. In areas of the world where humans, birds, and pigs are in close proximity to each other, it is easy for the viruses that prefer each of these species to mix together, as will be discussed below.
Here is a link to click on to see a depiction of the surface of the influenza virus:
(I need to figure out how to embed pictures into the blog. My apologies.)
The viral surface has been simplified to show only the H and N proteins. The genetic material consists of 8 strands of RNA. When the virus reproduces, the RNA floats freely in the mammalian host cell. New viruses form a coat (the envelope) around 8 strands of RNA to form new virus particles. You can imagine that if there are 2 different viruses present in the infected animal (or person), the 8 strands of RNA from one virus can mix with the 8 strands from the second virus, giving rise to new viruses containing different numbers of RNA strands from each virus; for example, 1 strand from virus 1 and 7 strands from virus 2; or 5 strands from virus 1 and 3 strands from virus 2. If one of the viruses is the highly lethal but not infectious avian flu (H5N1) and the other is a regular seasonal flu strain that is very contagious but not very lethal (e.g., H3N2), we could see the formation of a very contagious and very lethal new virus with different characteristics of either parent virus.
Now, what do the H and N proteins do? Both of them mediate the attachment of the virus to respiratory tract epithelium. The hemaglutinin binds to sialic acid residues on the lining cells of the respiratory tract. Different animals have different sialic acid configurations on the surfaces of the respiratory tract lining cells. For example, bird and human sialic acids differ in capablility to bind to H proteins on the influenza virus. That is what makes some viruses more easily infect one species of animal than another. The sialic acid in pigs easily binds H subtypes that are present on viruses that are spread both from person to person and from bird to bird. Once in the pig, reassortment of the RNA strands encoding the H proteins from birds and humans, can result in viruses now capable of easily infecting the other species. Thus, when escaping from the pig host, the new influenza virus might now more easily infect humans, yet possess the same virulence of the avian influenza virus. This is how epidemics and pandemics are born.
Neuraminidase, the N protein, cleaves sialic acid residues, thereby releasing the bound virus particle (via the H protein), allowing the virus to penetrate into the host cell. Thus both H and N proteins are responsible for the binding of influenza virus to the host cell, mediating the fusion with the host cell membrane and releasing the virus to the inside of the host cell so that the virus can reproduce.
You can see an animated video of this here: http://www.hhmi.org/biointeractive/animations/subunit/sub_middle_frames.htm
You will need to keep hitting the play button to get through the short video. A Google search of animation of influenza virus reproduction will get you to other animations of this process.
There is much more that is known about the influenza virus. This very, very short primer will make you aware of the significance of H and N proteins in the nomenclature of this pathogen.
Posted by DrSugar on 10/06/2011 at 11:08 AM
Cantaloupes. As if we have not had enough food borne illnesses. Hot dogs, sprouts, tomatoes, macaroni salads, and now cantaloupes. The CDC has reported that there have been at least 72 cases and 13 deaths of listeriosis, a bacterial infection that can be acquired from various foods. The reported cases have all developed after August 4. The end date of this outbreak has not yet been determined. Listeriosis is particularly serious in pregnant woman and those with compromised immune systems. People in 14 states, including New Mexico, Texas, and Colorado have become ill after having eaten cantaloupes grown in Colorado. So far, one case has been diagnosed in California. The fruit in question was grown at Jensen Farms, Holly Colorado, in the Rocky Ford area of the state. Jensen has voluntarily recalled cantaloupes shipped from July 29 through September 10. These cantaloupes may have one of 2 stickers: a green and white sticker that says “Product of USA – Frontera Produce – Colorado Fresh – Rocky Ford Cantaloupe” or a gray, yellow and green sticker, reading “Jensen Farms – Sweet Rocky Fords.” No other farms have been identified as supplying infected fruits or vegetables. If you have cantaloupes with these labels, do not eat them and discard the melons after securing them in a plastic bag, so animals and others do not eat the fruit.
Listeriosis is caused by the bacteria called Listeria monocytogenes and it can cause blood stream infection, meningitis or encephalitis, and fetal infection, resulting in miscarriage, still birth, and death of the fetus. It can be transmitted through a variety of foods including unpasteurized soft cheeses, hot dogs, deli meats, and now, cantaloupes. The illness can begin with diarrhea and other gastrointestinal complaints, followed by flu-like symptoms. Febrile gastroenteritis is a common presentation of listeriosis. Gastroenteritis typically spontaneously resolves within about 2 days. The elderly, pregnant women, and those with compromised immune systems are at greatest risk for developing invasive infection, and involvement of meninges and brain is particularly common in these situations. Treatment with antibiotics is very effective, but the infection needs to be considered so that proper therapy can be given.
CDC recommends the following to avoid infection with Listeria and other food borne pathogens:
- Rinse raw produce, such as fruits and vegetables, thoroughly under running tap water before eating. Dry the produce with a clean cloth or paper towel before cutting it up. This will help to prevent surface bacteria from following the knife through the melon.
- Thoroughly cook raw meat and poultry.
- Wash off countertops after they have contact with raw meat, poultry and other foods
- Heat hot dogs, deli meats, and cold cuts until they are steaming hot just before serving.
- Do not drink raw (unpasteurized) milk and do not eat fresh soft cheeses that have unpasteurized milk in them, especially Mexican-style cheeses like queso fresco.
- Be sure that your refrigerator is at or below 40 degrees F and your freezer is at or below 0 degrees F by using a refrigerator thermometer.
We will provide updates as needed as this outbreak unfolds and is eventually contained.
Posted by DrSugar on 09/30/2011 at 10:15 AM
Since we are entering the influenza virus season, we thought it appropriate to start with influenza as a topic. As you know, because immunity induced by influenza vaccine is transient, lasting only about a year, we are obligated to be vaccinated every year. Each year the virus changes its antigenic structure. This year’s vaccine contains 2 influenza type A viruses: the H1N1 virus, the virus responsible for the 2009 pandemic, plus the H3N2 virus; and an influenza B virus. All 3 of these viruses were in the vaccine used during last year’s flu season.
There have been many developments concerning influenza viruses this past year. There has been low level activity with the H1N1 pandemic strain throughout the world. However, there have been additional cases of H5N1 (avian influenza) in Asia. This virus has not been terribly contagious from person to person, but cases have occurred. This virus is characterized by a high mortality rate. If person to person transmission becomes more efficient, this virus could result in a very serious situation. The World Health Organization is following this virus very closely, paying particular attention to the possibility of enhanced person to person transmission.
Another development has been with the circulating H3N2 virus. This virus is known as swine flu, because it naturally circulates in the pig population. Two children, one in Indiana and the other in Pennsylvania were recently reported to have been infected with this virus. What makes this noteworthy, though, is that one of the 8 genes in the virus was identical to the H1N1 2009 pandemic influenza virus. This is an example of the influenza virus “re-assorting” its genes. This means that an animal, most likely a pig, was infected with several influenza viruses and in the course of these viruses reproducing, their DNAs got mixed up and repackaged together, making a virus with a unique DNA makeup. Only one of these 2 children had direct contact with swine and both recovered from their illness. The possibility of animals, particularly birds and swine, being infected with more than one influenza virus at the same time makes the generation of these new mutant strains of virus possible and it can make a virulent but less contagious virus much more likely to be spread from person to person. This is a first step in the generation of massive worldwide infections, such as the pandemic of 2009.
In future posts, we will discuss how influenza viruses are named and how they change their antigenic identity so easily. We will also be discussing MRSA, infection control and prevention practices, infectious diseases and travel medicine, and many other topics of interest. In the meantime, welcome to our blog. If there are topics you would like to see covered let us know. And, remember: wash your hands!
Alan M. Sugar, M.D.
Posted by DrSugar on 09/26/2011 at 11:27 AM
People interested in healthy eating frequently turn to sprouts as healthy food. Recent information from the CDC and other sources, however, suggests otherwise. In fact, sprouts have been shown to be an excellent purveyor of E. coli, specifically, Shiga toxin producing E. coli. The Shiga toxin is one of the factors produced by Shigella, allowing it to cause a severe infectious dysentery. E. coli carrying the gene for the production of this toxin are likewise serious enteric pathogens and have been associated with serious illness in people infected as a result of eating sprouts. And if that wasn’t enough, Salmonella and Listeria have also been found to be present on sprouts and responsible for food borne illness secondary to eating these contaminated vegetables. Unfortunately, it is impossible to wash these bacteria off of contaminated sprouts.
Since 1998, CDC has identified more than 30 outbreaks associated with sprouts of various sorts. The last remarkable outbreak was just this past summer, in Germany, where 4000 people became ill, more than 900 cases of hemolytic uremic syndrome were diagnosed, and 50 people died. Certain populations, pregnant women, young children, older adults, and those with immunocompromise are at increased risk of serious illness and death. Simply having the sprouts on your plate as a garnish is enough to spread the bacteria to the food you actually eat. For those of us who want to eat “healthy”, it is time to reconsider sprouts.
Alan M. Sugar
Posted by DrSugar on 09/26/2011 at 11:11 AM
|Blog Owner Profile
Alan Sugar, MD
Board Certified specialist in Infectious Diseases
Dr. Sugar is a graduate of Jefferson Medical College and completed his Internal Medicine Residency at Temple University Hospital and Santa Clara Valley Medical Center in San Jose California. Dr. Sugar completed his Infectious Diseases Fellowship at Stanford University. Since completing his fellowship in 1983, Dr. Sugar has been on faculty as Professor of Medicine at Boston University School of Medicine and has been staff physician at Cape Cod Hospital in Hyannis, Massachusetts, where he has also served as the Director of the HIV/AIDS program and Infectious Diseases Clinical Services.
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