# 9078
Anyone who watched last week’s PBS Frontline: The Ebola Outbreak saw several areas inside an MSF Ebola treatment center in Sierra Leone. Today Médecins Sans Frontières has published an interactive graphic (hover over areas to pop up pictures and descriptions) showing the individual components of a facility operating in a high risk area.
Follow this link to the fully interactive graphic of the static picture below, and this link for more on MSF’s work fighting the Ebola Epidemic.
# 8918
Although there are no FDA approved specific treatments for Ebola infection, it has been widely reported that two Americans afflicted with the virus have been given – and may have benefited from - an experimental drug cocktail called ZMapp (see CIDRAP News Report Experimental Ebola drug may have helped 2 US patients).
While early results are encouraging, ZMapp is extraordinarily difficult to produce in quantity, and in very short supply. According to a WaPo report from last night (see Can we give that experimental Ebola drug to West African victims?), NIH Director Anthony Fauci is quoted as saying:
“The number of doses that are available right now, today…is less than a handful. It really is going to be a supply problem. It would take months to produce a significant amount more.”
And of course, with only anecdotal (and very preliminary) data from two human recipients, there are no guarantees that this drug will prove both safe and effective in the long run across a larger cohort of patients. There has also been talk of a the development of a a vaccine against Ebola, with hopes to begin enrollment for a Phase I clinical trial as early as this fall, although years of testing likely lay ahead.
Given the extraordinary interest in ZMapp, and other experimental treatments and vaccines for Ebola, the CDC published a FAQ last night on the subject.
Questions and Answers on experimental treatments and vaccines for Ebola
This FAQ addresses questions the public has about potential treatments and vaccines for Ebola.
For further information on drug development, approval process, and research please contact the appropriate agency:
FDA media office: fdaoma@fda.hhs.gov
NIH media office: niaidnews@niaid.nih.gov
CDC media office: media@cdc.gov
ASPR media office: Gretchen.Michael@hhs.govWhat is ZMapp?
ZMapp, being developed by Mapp Biopharmaceutical Inc., is an experimental treatment, for use with individuals infected with Ebola virus. It has not yet been tested in humans for safety or effectiveness. The product is a combination of three different monoclonal antibodies that bind to the protein of the Ebola virus.
How effective is the experimental treatment?
It is too early to know whether ZMapp is effective, since it is still in an experimental stage and has not yet been tested in humans for safety or effectiveness. Some patients infected with Ebola virus do get better spontaneously or with supportive care. It's important to note that the standard treatment for Ebola remains supportive therapy.
This consists of the following measures:
- balancing the patients' fluids and electrolytes;
- maintaining their oxygen status and blood pressure; and
- treating them for any complicating infections.
Why aren't more people getting ZMapp?
At this time, very few courses of this experimental treatment have been manufactured. Since the product is still in an experimental stage, it is too early to know whether ZMapp is effective. The manufacturer of this experimental treatment continues to research and evaluate the product's safety and effectiveness. It has not yet been tested in humans for safety or effectiveness and much more study is needed.
Did the NIH play a role in getting the experimental therapy to the two U.S. patients in Liberia?
This experimental treatment was arranged privately by Samaritan's Purse, the private humanitarian organization, which employed one of the Americans who contracted the virus in Liberia. Samaritan's Purse contacted the Centers for Disease Control and Prevention (CDC), who referred them to the National Institutes of Health (NIH). NIH was able to provide the organization with the appropriate contacts at the private company developing this treatment. The NIH was not involved with procuring, transporting, approving, or administering the experimental treatments.
Will patients in West Africa be able to access this experimental treatment? How much supply is there?
The product is still in an experimental stage, and the manufacturer reports that there is a very limited supply, so it cannot be purchased and is not available for general use. The manufacturer has been planning for phase 1 clinical trials and does not have the capacity to manufacture large quantities of the treatment. The drug has not gone through clinical trials, meaning its safety and effectiveness has not yet been tested in humans. The manufacturer of the experimental treatment continues to research and evaluate the product's safety and effectiveness.
Is ZMapp available under the Food and Drug Administration's expanded access to investigational drugs?
Currently there are only experimental treatments for Ebola virus infection in the earliest stages of development. When a drug is not approved, the FDA can authorize access to potentially promising products through other mechanisms, such as through an emergency Investigational New Drug (IND) application. In order for an experimental treatment to be administered in the U.S., such a request must be submitted to and authorized by the FDA. The FDA cannot comment on the specifics of ongoing drug development programs and cannot reveal information that is not otherwise public concerning submissions covering such programs such as IND applications submissions. The FDA stands ready to work with companies and investigators treating these patients.
Is ZMapp a vaccine?
No. ZMapp is being developed as a therapeutic product for treatment of people infected with Ebola virus, but not to prevent infection in the same manner as a vaccine. The best way to prevent infection currently is with stringent infection control measures.
What's the difference between therapy and vaccine?
Vaccines are usually given to people before they are exposed to a virus or bacteria that causes a disease. A vaccine stimulates the immune system to generate antibodies and cellular immunity that can fight off an infection if it were to occur. Typically, therapeutics are provided to people who are already infected with the virus. With the experimental ZMapp treatment, the monoclonal antibodies bind to the virus, so that the human immune system can clear the virus.
Are there Ebola vaccines available for use or in development?
There are currently no FDA approved vaccines for Ebola. The NIH's National Institute of Allergy and Infectious Diseases is working on developing an Ebola vaccine. NIH recently announced they are expediting their work, and aiming to launch phase 1 clinical trials of an Ebola vaccine in the fall. NIH is also supporting the Crucell biopharmaceutical company in its development of an Ebola/Marburg vaccine as well as Profectus Biosciences in its development of an Ebola vaccine. Additionally, NIH and the Thomas Jefferson University are collaborating to develop a candidate Ebola vaccine based on the established rabies vaccine.
Is the U.S. government involved in the development of ZMapp?
The U.S. government, specifically, the NIH's National Institute of Allergy and Infectious Diseases, the Department of Defense's Defense Threat Reduction Agency (DTRA), and the HHS' Biomedical Advanced Research and Development Authority (BARDA), has provided support for the development of this experimental treatment.
Are there other companies developing experimental treatments or vaccines?
Two other companies, Tekmira and Biocryst Pharmaceuticals, receive funding from the Department of Defense's Defense Threat Reduction Agency and have therapeutic candidates for Ebola in early development. The Department of Defense is working with a company called Newlink to develop an Ebola vaccine candidate. BioCryst, with NIH support, is working to develop an antiviral drug to treat Ebola virus that is expected to begin Phase 1 testing later this year.
# 8485
Three years ago, in the movie `Contagion’, a MERS-like virus (dubbed MEV-1) emerged in China and spread quickly around the globe while scientists at the CDC (and elsewhere) worked frantically to find a vaccine. Unlike most summer blockbusters, this film endeavored to portray the science as accurately as possible (see my review here).
One area where the movie took some dramatic license was in portraying the development (and deployment) of a vaccine for this never-before-seen virus as happening over a matter of months, rather than years.
As with most novels, TV shows and movies that deal with an epidemic outbreak, there is a need to `wrap up’ the story in the last 15 minutes. The standard solution therefore is for valiant scientists to come up with a last-minute cure, and for it to be dispensed immediately on a global scale in order to save civilization.
It’s a nice fantasy, but with today’s technology, that’s about all it is.
A quick vaccine – and by quick, I mean available any time in the next several years – to the MERS virus seems unlikely, given the realities of vaccine development, testing, and production. The cost of development could run into the hundreds of millions of dollars, and given that researchers have been working for more than a decade on creating SARS vaccine – success is far from assured.
Nevertheless,the Saudi Ministry of Health made a big point to assure the public yesterday that they were going to `invite international companies to the vaccine industry to conduct research to find cures for the virus’.
One possible hitch to creating a vaccine – at least for use in camels –was revealed earlier this week in EID Journal: MERS Coronavirus In A Saudi Dromedary Herd, where we learned that elevated antibody titers from previous exposures don’t appear to be very protective against reinfection with the MERS virus.
That doesn’t mean there aren’t some avenues of research that might produce – if not a vaccine – some form of treatment for MERS infection. So today, a brief review of some of the pharmacological options, and the obstacles that must be overcome,before they can be used.
With no coronavirus-specific antiviral in our arsenal, treatment for infection has basically been supportive (e.g. fluids, vasopressors, ventilators and/or ECMO, dialysis, and antibiotics for secondary infections). While many people only suffer mild (or asymptomatic) infection, among those most severely affected, the mortality rate runs over 50%.
During the SARS epidemic a decade ago, the early administration of Ribavirin was associated with a better outcome (see CMAJ Ribavirin in the treatment of SARS: A new trick for an old drug?), but the number of patients treated in this way was fairly small and the results far from conclusive.
Although Ribavirin use has been associated with significant side effects, it has the decided advantage of already being approved for human use.
Last summer, in Nature: Animal Testing Of Drug Combo Shows Potential For Treating MERS, we looked at early work that suggested a combination of Interferon-α2b & ribavirin – which showed promise earlier that year in in-vitro experiments - `reduced virus replication, moderated the host response, and improved the clinical outcome’ of rhesus macaques experimentally infected with the MERS coronavirus.
. At the time I cautioned that, while encouraging, the following caveats should be kept in mind:
Fast forward to January of this year (see JID: Early Observational Study On Ribavirin & Interferon Treatment of MERS-CoV) and the results from treating humans with this drug combo were far from encouraging: The authors wrote:
Conclusions
While ribavirin and interferon may be effective in some patients, our practical experience suggests that critically ill patients with multiple comorbidities who are diagnosed late in the course of their illness may not benefit from combination antiviral therapy as preclinical data suggest. There is clearly an urgent need for a novel effective antiviral therapy for this emerging global threat.
Not exactly a rousing success, but then these were critically ill patients (all on ventilators) with profound comorbidities (4 on maintenance dialysis), and treatment was begun (on average) 19 days into their illness.
Essentially, at that stage of their illness, attempts to use this, or any other antiviral therapy, was pretty much a long shot. It remains to be seen whether further testing will bear out its value.
An investigational drug – BCX4430 – was the subject of a letter in the Journal Nature last month, that holds some promise as a treatment for filovirus infections (Ebola, Marburg). As an aside, the manufacturer – Biocryst –stated in their press release:
In addition, BCX4430 was shown to be active in vitro against a broad range of other RNA viruses, including the emerging viral pathogen Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
Still, this drug is a long way from being approved for human use, and its effect on the MERS virus – for now - is speculative at best.
The therapeutic option with perhaps the most promising future is the use of Convalescent Plasma, taken from patients who have already recovered from infection. Three years ago , in CID Journal: Convalescent Plasma Therapy For Severe H1N1, I described the process:
Blood is collected from people that have been infected and have recovered, and through a process called plasmapheresis, the blood cells are removed leaving only blood plasma.
This is done by passing the blood through a special filter, or by using a centrifuge. The remaining blood plasma will contain antibodies that could then be injected into severely ill patients.
Convalescent plasma could, theoretically, be used as either a treatment for someone already infected, or as a temporary prophylactic, to prevent infection.
There is more to it, of course.
The donor must be checked for a variety of blood borne diseases (i.e. hepatitis B, hepatitis C, Syphilis, and HIV), and then the plasma is usually heated to inactivate other possible pathogens.
The idea of using convalescent serum for MERS goes back almost a year; This is from the World Health Organization Novel coronavirus summary and literature update – as of 8 May 2013.
An international network of clinical experts has been convened to discuss therapeutic options. It concluded that in the absence of clinical evidence for disease-specific interventions, convalescent plasma is the most promising therapy. A memo containing advice for setting up international or regional serum centers, to obtain and share convalescent plasma, has been circulated by WHO to ministries of health in affected countries. WHO and the International Severe Acute Respiratory and Emerging Infection Consortium have developed and shared a set of research protocols and case report forms to help clinical investigators establish studies of pathogenesis and pharmacology. These are available at http://www.prognosis.org/isaric/.
Last month the WHO released a Position Paper on Collection and Use of Convalescent Plasma or Serum as an Element in Middle East Respiratory Syndrome Coronavirus Response Pdf, 70kb, which concluded:
The WHO Blood Regulators Network recommends that scientific studies on the feasibility and medical effectiveness for collection and use of convalescent plasma or serum be explored through clinical trials. In particular, an opportunity exists to study the feasibility, safety and effectiveness of convalescent plasma or serum and possibly other passive immunotherapies in MERS-CoV. Acting within their mandates, regulatory agencies can play an essential role to enable progress in this area. Countries which want to engage in this type of practice should take all necessary steps to establish appropriate regulatory conditions for the collection of convalescent plasma or serum, the conduct of clinical studies and the monitoring and reporting of patient outcomes.
Programmes conducted at the national level should ensure the use only of convalescent plasma or serum collections that meet the safety, quality and efficacy criteria consistent with established regulatory standards. The feasibility of production on a large scale, possibly including a specific immunoglobulin, should be considered based on the outcome of studies, the course of the epidemic, and the available infrastructure for manufacturing under GMP.
Making headlines, and sparking a great deal of Arabic twitter traffic, have been the claims of a Saudi researcher Dr Faten Khurshid, who proposes that serum antibodies could be harvested from camels, along with camel milk immune proteins, and then used to treat human infections.
Although equine serums have been used for more than a century (and still are), their use has declined in recent years due to concerns over adverse reactions, which according to the FDA, may include:
While likely an abundant source of serum antibodies, it is also likely that a camel derived product could suffer some of these same (and perhaps, other) adverse reactions.
So far, the Saudi MOH doesn’t appear to be terribly receptive to Dr.Khurshid’s proposal.
Additionally, research is ongoing into ways to block the receptor cells for MERS; Dipeptidyl peptidase 4 (DPP4). But once again, this avenue of research is in its infancy, and it may take years before an effective drug can be developed.
While the lack of a vaccine, or drug therapy, against the MERS virus is a serious concern, we are not exactly helpless in the face of this emerging virus.
Eleven years ago the SARS virus was far more widespread – and more transmissible – than the MERS virus of today, and yet it was quickly brought under control without the aid of a vaccine.
What it took was a recognition of the seriousness of the threat, a coordinated global public health response, stringent infection control protocols, and the effective use of quarantines and isolation (see SARS And Remembrance).
Solutions that are available today, but that will only work when there is full disclosure and broad cooperation between the various national and international entities charged with containing this virus.
A lesson learned the hard way by China with SARS in 2003, and one that hopefully won’t have to be relearned by other nations with MERS in 2014.
Coronavirus – Credit CDC PHIL
# 7743
One of the more worrisome aspects of the recent emergence of MERS coronavirus has been the lack of a specific and effective treatment. Unlike influenza, there are currently no coronavirus-specific antivirals available.
Treatment has basically been supportive (e.g. fluids, vasopressors, ventilators and/or ECMO, dialysis, and antibiotics for secondary infections).
Today, in a letter that appears in Nature Medicine, we learn that a drug combination (Interferon-α2b & ribavirin) – which showed promise earlier in the year in in-vitro experiments - `reduces virus replication, moderates the host response, and improves the clinical outcome’ of rhesus macaques experimentally infected with the MERS coronavirus.
While welcome news, a few caveats are in order.
Still, this has to be seen as progress. I’ve a link to the Abstract, a brief announcement from NIAID, then a link to Helen Branswell’s article on this announcement.
Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques
Darryl Falzarano, Emmie de Wit, Angela L Rasmussen, Friederike Feldmann, Atsushi Okumura,Dana P Scott, Doug Brining, Trenton Bushmaker, Cynthia Martellaro, Laura Baseler, Arndt G Benecke, Michael G Katze, Vincent J Munster& Heinz Feldmann
ABSTRACT (Excerpt)
The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro6; therefore, we initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to untreated, infected macaques, treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs.
Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-α2b and ribavirin should be considered for the management of MERS-CoV cases.
From NIAID:
Sunday, September 8, 2013
MERS-CoV Treatment Effective in Monkeys, NIH Study Finds
WHAT:
National Institutes of Health (NIH) scientists report that a combination of two licensed antiviral drugs reduces virus replication and improves clinical outcome in a recently developed monkey model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Their study, which appears as a letter in the Sept. 8 edition of Nature Medicine, expands on work published in April showing that a combination of ribavirin and interferon-alpha 2b stops MERS-CoV from replicating in cell culture. Both antivirals are routinely used together to treat viral diseases such as hepatitis C.
In the latest study, investigators at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) infected six rhesus macaques with MERS-CoV and, eight hours later, treated half of them with the two-drug regimen. Compared to the untreated animals, the treatment group showed no breathing difficulties and only minimal X-ray evidence of pneumonia. The treated animals also had lower amounts of virus and less severe tissue damage in the lungs.
As of Aug. 30, 2013, the World Health Organization has reported 108 human cases of MERS-CoV infection, including 50 deaths. Given the current lack of treatment options, the authors of this study conclude that combined ribavirin and interferon-alpha 2b therapy should be considered as an early intervention.
And finally, from Helen Branswell, a detailed and informative report, with comments from Matthew Frieman, Professor of Virology at the University of Maryland medical school in Baltimore.
Drug combo helps reduce MERS virus in animals: study
Helen Branswell, The Canadian Press
Published Sunday, September 8, 2013 1:16PM EDTTORONTO -- New research is adding weight to the idea that a combination of existing drugs may help some patients infected with the new MERS coronavirus.
The findings could prove to be important because there is no vaccine to prevent the infection and no drugs specifically designed to mitigate the damage it does in severe cases.
Infections with the new virus continue to pile up, particularly in Saudi Arabia.
Photo Credit USGS – Wastewater: The Primary Treatment Process
1. Screening 2. Pumping 3. Aerating 4. Removing sludge 5. Removing Scum 6. killing bacteria
# 6699
While it may not seem (or even be) glamorous, there are scientists who spend considerable time examining the input and output of wastewater (sewage) treatment plants. Given the potential environmental impact of the discharges from these facilities, it is important work.
The subject of wastewater treatment plants - and the substances that their processes can fail to remove during treatment - has come up before in this blog.
In 2007, with governments around the world stockpiling large quantities of Tamiflu (Oseltamivir) in anticipation of a pandemic, concerns turned to what would happen if millions of doses were dispensed, consumed, and excrete by humans into the waste water system in a short period of time.
In The Law of Unintended Consequences we looked at a report in Environmental Health Perspectives (EHP) called Potential Risks Associated with the Proposed Widespread Use of Tamiflu that found enough of excreted oseltamivir carboxylate (OC) would survive treatment, and be ejected into the environment, to raise concerns.
In October of 2009 and we saw another report (see Everything Old Is News Again), based on studies done the previous year in Kyoto, Japan – that showed elevated levels of the OC Metabolite in wastewater discharge.
In 2011, in Pandemics & The Law Of Unintended Consequences we saw yet another study that looked at potential problems inherent in the massive distribution and consumption of antibiotics and antivirals during a pandemic.
WWTPs (Wastewater Treatment Plants) depend upon microbial activity in order to breakdown or `digest’ sewage.
Antibiotics in the sewage – at elevated levels such as might be seen during a pandemic – could inhibit microbial activity, resulting in the failure of WWTPs and the discharge of under-treated wastewater into the environment.
Today, a new study, this time on MRSA (methicillin-resistant Staphylococcus aureus) and how it fares in the wastewater treatment process. As many WWTPs provide reclaimed water for irrigation use, the concern is that MRSA shed in feces might make it through the plant and into the environment.
The University of Maryland-led study study appears as an open access article that appears in Environmental Health Perspectives.
Methicillin-Resistant Staphylococcus aureus (MRSA) Detected at Four U.S. Wastewater Treatment Plants
November 1, 2012 Research
Rachel E. Rosenberg Goldstein, Shirley A. Micallef, Shawn G. Gibbs, Johnnie A. Davis, Xin He, Ashish George, Lara M. Kleinfelter, Nicole A. Schreiber, Sampa Mukherjee, Amir Sapkota, Sam W. Joseph, and Amy R. Sapkota
Abstract
Background: The incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections is increasing in the United States, and it is possible that municipal wastewater could be a reservoir of this microorganism. To date, no U.S. studies have evaluated the occurrence of MRSA in wastewater.
Objective: We examined the occurrence of MRSA and methicillin-susceptible S. aureus (MSSA) at U.S. wastewater treatment plants.
Methods: We collected wastewater samples from two Mid-Atlantic and two Midwest wastewater treatment plants between October 2009 and October 2010. Samples were analyzed for MRSA and MSSA using membrane filtration. Isolates were confirmed using biochemical tests and PCR (polymerase chain reaction). Antimicrobial susceptibility testing was performed by Sensititre® microbroth dilution. Staphylococcal cassette chromosome mec (SCCmec) typing, Panton-Valentine leucocidin (PVL) screening, and pulsed field gel electrophoresis (PFGE) were performed to further characterize the strains. Data were analyzed by two-sample proportion tests and analysis of variance.
Results: We detected MRSA (n = 240) and MSSA (n = 119) in 22 of 44 (50%) and 24 of 44 (55%) wastewater samples, respectively. The odds of samples being MRSA-positive decreased as treatment progressed: 10 of 12 (83%) influent samples were MRSA-positive, while only one of 12 (8%) effluent samples was MRSA-positive. Ninety-three percent and 29% of unique MRSA and MSSA isolates, respectively, were multidrug resistant. SCCmec types II and IV, the pvl gene, and USA types 100, 300, and 700 (PFGE strain types commonly found in the United States) were identified among the MRSA isolates.
Conclusions: Our findings raise potential public health concerns for wastewater treatment plant workers and individuals exposed to reclaimed wastewater. Because of increasing use of reclaimed wastewater, further study is needed to evaluate the risk of exposure to antibiotic-resistant bacteria in treated wastewater.
Environ Health Perspect 120:1551–1558 (2012). http://dx.doi.org/10.1289/ehp.1205436 [Online 6 September 2012]
The full report runs 8 pages, and can be download here.
A summation of this research is available from the University of Maryland’s School of Public Health. I’ve cut to the chase with the excerpts posted below, so follow the link to read the full story.
The School of Public Health News
November 5, 2012
NEWS RELEASE
Contact: Kelly Blake, kellyb@umd.edu, 301-405-9418Superbug MRSA Identified in U.S. Wastewater Treatment Plants
University of Maryland-led study is first to document environmental source of the antibiotic-resistant bacteria in the United States
<SNIP>
They found that MRSA, as well as a related pathogen, methicillin-susceptible Staphylococcus aureus (MSSA),were present at all four WWTPs, with MRSA in half of all samples and MSSA in 55 percent.MRSA was present in 83 percent of the influent-- the raw sewage--at all plants, butthe percentage of MRSA- and MSSA-positive samples decreased as treatment progressed. Only one WWTP had the bacteria in the treated water leaving the plant, and this was at a plant that does not regularly use chlorination, a tertiary step in wastewater treatment.
Ninety-three percent of the MRSA strains that were isolated from the wastewater and 29 percent of MSSA strains were resistant to two or more classes of antibiotics, including several that the U.S. Food and Drug Administration has specifically approved for treating MRSA infections. At two WWTPs, MRSA strains showed resistance to more antibiotics and greater prevalence of a gene associated with virulence at subsequent treatment stages, until tertiary chlorination treatment appeared to eliminate all MRSA. This suggests that while WWTPs effectively reduce MRSA and MSSA from influent to effluent, they may select for increased antibiotic resistance and virulence, particularly at those facilities that do not employ tertiary treatment (via chlorination).
“Our findings raise potential public health concerns for wastewater treatment plant workers and individuals exposed to reclaimed wastewater,” says Rachel Rosenberg Goldstein, environmental health doctoral student in the School of Public Health and the study’s first author. “Because of increasing use of reclaimed wastewater, further research is needed to evaluate the risk of exposure to antibiotic-resistant bacteria in treated wastewater.”
Most WWTPs are designed to efficiently remove solids and to disinfect discharge water, but do less well when it comes to removing chemicals.
Although only four plants were studied in this project, the results suggest that plants that fail to chlorinate routinely may be at greater risk of letting antibiotic resistant bacteria back into the environment.
Whether it is antiviral or antibiotic metabolites, remnants from illicit drug use, or resistant organisms themselves, what comes out of these treatment plants can affect our environment, and our population.
On a planet with 7 billion people, figuring out how to safely dispose of, recycle, or treat human waste has become a major challenge.
Shortcomings in WWTP systems – even seemingly small ones - can pose serious public health risks, including potentially creating and spreading resistant bacterial organisms.
As the authors of this study concluded, more research is now needed to evaluate and quantify the risk.
# 4318
IgG2 or immunoglobulin G subclass 2 are a type of antibody that our immune system produces to fight off invading pathogens. There are 4 type of IgG antibodies, and together they form the bulwark of our defense against bacterial and viral infection.
Last September Australian researchers discovered what they believed was a link between low levels of IgG2 and the severity of H1N1 infection.
In this report from last summer, Jason Gale of Bloomberg News brings us an early glimpse at this research.
Swine Flu Pregnancy Danger Tied to Cell Virus-Fighter (Update1)
By Jason Gale
Sept. 15 (Bloomberg) -- Pregnant women may be more vulnerable to swine flu because an infection-fighting blood cell fails to do its job within this group, Australian doctors said.
The finding emerged after doctors in Melbourne analyzed blood tests to determine why pregnant women made up a majority of their critically ill H1N1 patients. The results, reported at a medical meeting in San Francisco, showed six of seven of the women lacked a cell protein known as immunoglobulin G subclass 2, or IgG2. The antibody deficiency also was noted in seriously ill nonpregnant patients.
Today, in a follow up to that discovery, researchers are coming forth with a study that they say provides some insight into why novel H1N1 can be so severe in a small percentage of cases, and a possible course of treatment.
Researchers pinpoint swine flu death risk
AAPLast updated 00:00 04/02/2010
Australian researchers have found a way to predict whether a person's dose of swine flu is likely to turn life threatening, in a globally significant development.
Melbourne-based Professor Lindsay Grayson said it offered doctors a means to flag those patients who were most likely to experience the worst complications from a swine flu infection.
The discovery also pointed to a potential new treatment and an explanation for the most puzzling aspect of the global A(H1N1) pandemic.
That was, Prof Grayson said, the virus's ability to be a "pretty mild disease" for the majority while also striking young and apparently healthy people.
"The unusual thing about swine flu is that, if you compare it to seasonal influenza, it mainly affects people aged 15 to 35," said Prof Grayson, who is director of infectious diseases at Austin Health.
"It's very unusual for us to see a 22-year-old about to die with (ordinary seasonal) influenza.
"Our thought is there is something special about swine flu and its interaction with immunoglobulin."
Prof Grayson found those swine flu patients who become the sickest were likely to have a pre-existing deficiency of a specific blood protein (immunoglobulin G2 or IgG2) that is crucial to the proper functioning of the immune system.
The study, which is to be published in the journal Clinical Infectious Diseases, does not appear to be available online yet.
# 4112
Shanghai health authorities are asking those who have been vaccinated against the H1N1 virus to donate blood so they can create a serum to treat seriously ill patients.
If all of this sounds vaguely familiar to you, it may be because we’ve discussed this process in the past. Two years ago, in fact, in a blog entitled Human Serum For Bird Flu?
Since that time, we’ve heard of several attempts in China to treat seriously ill bird flu patients with convalescent serum. While some successes have been reported, not all have had positive outcomes.
First today’s article from the Shanghai Daily, then we’ll revisit the subject.
City calls for blood in swine-flu war
By Cai Wenjun | 2009-12-3 |
SHANGHAI health authorities yesterday launched their latest drive in the fight against swine flu, calling on people who have been vaccinated against the virus to donate blood for emergency-treatment storage.
First in the queue will be 34 inoculated medical staff at the Shanghai Public Health Clinical Center, who are expected to donate blood today.
City blood-collection authorities said that general donations were also welcome as supplies were low, particularly of types A and O.
According to experts, a person starts to produce antibodies three weeks after catching swine flu or two weeks after vaccination.
Blood from these people can then be used to treat patients seriously affected by the H1N1 virus.
"Using serum from vaccinated staff to treat serious cases is mentioned in a treatment guide issued by the Ministry of Health," said Dr Lu Hongzhou, a member of city's expert panel on swine-flu treatment - and one of the 34 expected donors.
"The technology is safe and we have used it on our patients with good results," Lu said.
Harvesting serum antibodies from someone who has been vaccinated, or who has contracted a disease and recovered, is not a new idea. In fact the first controlled clinical trial, Fibiger’s trial of serum treatment of Diptheria, dates back to 1898.
During the great pandemic of 1918, serum treatments were tried, but the results were often disappointing.
In recent years Chinese scientists have suggested infecting horses with an attenuated (weakened) H5N1 and producing a serum.
The process is relatively simple. Once someone (or an animal) is able to produce antibodies, a quantity of blood can be removed and through a process called plasmapheresis, the blood cells are removed from the blood plasma.
This is done by passing the blood through a special filter, or by using a centrifuge. The blood plasma will contain antibodies that could then be injected into people.
A serum could, theoretically, be used as either a treatment for someone already infected, or as a prophylactic, to prevent infection.
There are problems involved, however.
It takes a large amount of blood product to produce a small amount of serum. Human donors would have to be screened for AIDS and Hepatitis, among other blood borne diseases.
Horse serum is still used today, although sparingly, because of `serum sickness’, a reaction to the serum that can be fatal.
And lastly, a serum is not a vaccine. It confers a temporary immunity, not a permanent one.
A PLoS One study from August of 2008 followed the treatment, and course of illness, of 26 Chinese H5N1 patients. Convalescent plasma – or serum – was tried with success on a couple of them.
Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China
Out of 26 patients in this study, 17 (65%) died.
While antiviral therapy was the primary treatment, Two patients also received experimental blood plasma from previously infected survivors of the H5N1 virus.
From the PLoS Study.
Experimental Treatment
Two critically ill adult H5N1 cases (31-year-old male, 44-year-old female) with ARDS were treated with convalescent plasma obtained from one of two fully recovered H5N1 adult donor cases.
Plasma was obtained 129 days after illness onset from an adult female case and 81 days after illness onset from an adult male case. Both donors' convalescent plasma tested negative for hepatitis B, hepatitis C, and HIV, and were separated and heat-inactivated at 56°C for 10 h before transfusion.
The male ARDS case received three units (200 mL/unit) of transfused convalescent plasma from the female donor for 2 days, beginning on illness day 13. His H5N1 viral titre in bronchial-alveolar lavage fluid declined substantially and was undetectable for the next 3 consecutive days after receipt of the third convalescent plasma dose.
The female ARDS case, who had a history of bronchiectasis, received one unit (200 mL) of transfused convalescent plasma from the male donor once daily for 3 days, starting on illness day 13. Further virological testing has not been done for this case. Both cases also received oseltamivir (75 mg po BID) on illness days 10–14 and days 8–12, respectively.
Both cases recovered fully and were discharged home.
Fascinating stuff, and hopefully we’ll get some good data out these trials in China.
# 4019
Yes, this is a reprint of one of my older blogs. But it's an important one. Perhaps even lifesaving.
While it was written with a severe influenza pandemic in mind, even a mild influenza can inflict serious illness on some of the population.
Staying hydrated is important, even with seasonal flu.
With pandemic flu surging in the northern hemisphere, today is a good day to repost it.
Dehydration, and severe diarrheal disease, particularly among children in the third world, is a massive killer. Recognizing this threat, more than 25 years ago the WHO (World Health Organization) came up with what is now called ORS, or an Oral Rehydration Solution.
Hundreds of millions of sachets, or packets of this powder, are shipped each year to various third world countries, and there is no doubt that their use has greatly decreased the loss of life due to cholera, dysentery, and other diseases.
In a Flu Pandemic, the need for ORS will be great throughout the world. In western societies, where modern medical care is common, IV’s are generally used instead of ORS. There are economic and psychological reasons for this, although many doctors argue that ORS would be just as effective for the majority of patients.
Dehydration, from a prolonged bout of flu; with it’s fever, vomiting, and diarrhea, can easily kill patients that might have otherwise survived the virus. As IV’s may well be in short supply, or simply unavailable during a pandemic, the use of ORS may well be the most beneficial treatment that most patients can receive. Certainly, with home care being the most likely venue for most patients, ORS will play a large role in the treatment of pandemic flu.
There are, however, conflicting opinions as to what constitutes the proper formula for making your own ORS. All formulas use a base of sugar and salt, in an appropriate ratio. Some formulas, however, add potassium and Sodium Bicarbonate.
A little Biochemistry
When the human body becomes dehydrated, it loses both water and essential electrolytes, particularly sodium. This condition can quickly become life threatening.
In the human body, fluids tend to move from a less salty environment to the saltier one. As an example, if someone drowns in fresh water, the water in the lungs is less salty than the blood, and so this water is quickly absorbed from the lungs into the surrounding tissues.
If a person drowns in salt water, the water in the lungs is saltier than the blood, and so additional fluid is pulled into the lungs to `dilute’ the salt water. In other words, the body tries to balance both sides of the equation.
This is an important concept when dealing with rehydration therapy.
Ingesting plain water does not help restore the salt content of the body. But ingesting water with too much salt will draw fluids from the body, and make the dehydration worse.
While many believe the exact ratios of sugar and salt to be writ in stone, the truth is, if you have to err, err on the side of less salt.
Sugar is added to the ORS solution for two reasons. First, it was discovered in the early 1960’s that sugar helped with the transport of fluids across the cellular membranes in the bowel. In 1977, the British Medical Journal Lancet called this `possibly the most important medical discovery of the 20th century’.
Sugar also provides needed calories, and as a carbohydrate, can help prevent ketoacidosis from occurring.
But, as with salt, too much sugar can be detrimental, it can promote diarrhea, and make the loss of fluids worse.
This is one concern regarding the use of sports drinks, such as gatoraid, for rehydration therapy. Many of these commercially available mixtures simply have too much sugar.
Making your own ORS
The bottom line, of course, is how to make a cheap, safe, and effective ORS powder yourself.
The simplest formula is 3 Tablespoons of sugar, and 1 teaspoon of salt, dissolved in 1 quart of potable water.
An alternative simple formula is 8 teaspoons of sugar, and 1 teaspoon of salt, dissolved in 1 quart of potable water.
This basic formula has been used effectively for more than 30 years by WHO, UNICEF, and other relief agencies and has saved millions of lives.
Over the past year, there has been some debate over the amount of salt and sugar in this formula. The old formula certainly works, and is safe. But some doctors have argued that a lower salt and sugar level might reduce fluid loss by curbing diarrhea.
I’ve elected to create single-serve packets of ORS powder, with each packet designed to be added to 1 liter of water. Two packets would be used for a 2-liter bottle.
I’ve located small, reclosable baggies, called bagettes sold at Michaels Art Supplies. You will find them in the bead section. Snack sized baggies, though lighter gauge plastic, would work as well. The small 2”x3” bagettes are just a little too small for the amount of powder required. You will need to go to the next size up, which are 3”x5”.
Along with these baggies, you will need table salt and sugar. I am electing to use non-iodized salt, although I am not aware of any reason why iodized salt would present a problem. The only other things you will need are measuring spoons and a felt tipped marker.
Into each baggie I am placing 3 TABLESPOONS of Sugar, and 1 TEASPOON of salt. These do not need to be mixed. I am writing on each Baggie “ORS POWDER- ADD TO 1 LITER OF WATER”.
This is the basic formula recommended by Dr. Grattan Woodson in his GOOD HOME TREATMENT OF INFLUENZA guide.
In his home medical guide, Dr. Woodson writes:
"Preventing or treating dehydration in people with flu will save more lives than any other intervention during the influenza pandemic."
Identification of dehydration
When patients have a fever, vomiting, and/or diarrhea, they lose much more water from the body than is commonly appreciated. Symptoms of dehydration include weakness, dizziness, headache, confusion, and fainting. Signs of dehydration include dryness of the mouth, decreased saliva, lack of or very small urine volume that is dark and highly concentrated, sunken eyes, loss of skin elasticity, low blood pressure, especially upon sitting up or rising from the sitting to the standing position, and fast pulse rate, especially when moving from the lying to sitting or standing positions
Since I make it a practice not to offer medical advice, I would refer you to to Dr. Woodson’s excellent guide for further guidance on the administration (when, how much, etc) of rehydration fluids.
While you are at it, take a look at the rest of the good doctor’s website for more home care information.
You may elect to add a flavoring to this mixture. Unsweetened Koolaid would add flavor and color, and make the drink more palatable to some. It might, however, prove to be an intestinal irritant to some people. I intend to leave mine unflavored, and will add koolaid to individual liters of solution if desired.
At 15 cents a gallon, the price is right. And for someone who is dehydrated, having this solution on hand can be lifesaving.
CAVEATS
You should never attempt to force fluids by mouth on anyone who is unconscious. An eye dropper may be used to slowly infuse liquids in semi conscious patients but there is a risk of choking.
Better to dilute this powder too much, than too little. DO NOT SKIMP ON THE WATER.
For more complete information on oral rehydration fluids visit the Healthlink Worldwide webpage at
# 3991
The World Health Organization has released revised guidance on the diagnosis and treatment of the H1N1 virus.
It may be downloaded from the WHO site:
Clinical management of human infection with new influenza A (H1N1) virus: revised guidance
Publication date: November 2009
Download the document [pdf 228kb]
This 15 page PDF document covers a wide range of issues. I’ve excerpted a few sections below, but download and read the whole document.
Risk factors for severe disease from pandemic (H1N1) 2009 virus infection reported to date are considered similar to those risk factors identified for complications from seasonal influenza.
- These include the following groups:
• Infants and young children, in particular <2 years
• Pregnant women
• Persons of any age with chronic pulmonary disease (e.g. asthma, COPD)
• Persons of any age with chronic cardiac disease (e.g. congestive cardiac failure)
• Persons with metabolic disorders (e.g. diabetes)
• Persons with chronic renal disease, chronic hepatic disease, certain neurological conditions (including neuromuscular, neurocognitive, and seizure disorders), hemoglobinopathies, or immunosuppression, whether due to primary immunosuppressive conditions, such as HIV infection, or secondary conditions, such as immunosuppressive medication or malignancy
• Children receiving chronic aspirin therapy
• Persons aged 65 years and older
A higher risk of severe complications from pandemic (H1N1) 2009 virus infection has also been reported in individuals who are obese (particularly in those who are morbidly obese) and among disadvantaged and indigenous populations.
On average, about 1/2 of hospitalized patients have had at least one or more underlying medical conditions1
. However, about 1/3 of patients with very severe illness admitted to ICU were previously healthy persons.
Infection control
Evidence to date suggests that pandemic (H1N1) 2009 virus is transmitted similarly to seasonal influenza A and B viruses. Appropriate infection control measures (Standard plus Droplet Precautions) should be adhered to at all times. Whenever performing high-risk aerosol-generating procedures (for example, bronchoscopy or any procedure involving aspiration of the respiratory tract) use a particulate respirator (N95, FFP2 or equivalent), eye protection, gowns, and gloves and carry out the procedure in an adequately ventilated room, either naturally or mechanically, as per WHO guidance 3
The duration of isolation precautions for hospitalized patients with influenza symptoms should be continued for 7 days after onset of illness or 24 hours after the resolution of fever and respiratory symptoms, whichever is longer, while a patient is in a health-care facility. For prolonged illness with complications (i.e. pneumonia), control measures should be used during the duration of acute illness (i.e. until the patient has improved clinically). Special attention is needed in caring for immunosuppressed patients who may shed virus for a longer time period and are also at increased risk for development of antiviral-resistant virus
(click images to enlarge)
# 3985
While the vast majority of H1N1 influenza victims recover quickly and without incident, a very small percentage go on to endure particularly serious and life-threatening symptoms – including ARDS (Acute Respiratory Distress Syndrome).
Last week, at the CHEST 2009 conference (Annual meeting of the American College of Chest Physicians), a study was presented on the results of an antiviral/steroid cocktail administered to ICU patients in Argentina during their recent pandemic wave.
This cocktail consisted of high dose oseltamivir (150mg twice a day), along with one of two steroids.
For those presenting with ARDS, they were given Methylprednisolone (Medrol) 1 mg/kg/day for 14 days. All other ICU patients received hydrocortisone 300 mg/day.
The administration of corticosteroids in ARDS has been tried in the past, with varying levels of success. The experience from SARS in 2003 and H5N1 in the middle of this decade showed short-term improvement, but long-term survival rates were less than encouraging.
In 2007 the WHO (World Health Organization) advised against the use of steroids in the treatment of Bird flu, stating:
Corticosteroid therapy has failed so far to show effectiveness, and prolonged or high dose corticosteroids can result in serious adverse events in H5N1 patients, including opportunistic infection. Corticosteroids should not be used routinely, except for persistent septic shock with suspected adrenal insufficiency.
But that was then. This is now.
I’ve excerpted some passages from a report on Doctor’s Guide that reviews the presentation at the CHEST 2009 Conference.
It is, admittedly, a small study. Only 13 patients. But the results are encouraging.
Follow the link to read it in its entirety.
By Betty S. Riggs
SAN DIEGO -- November 9, 2009 -- The combination of oseltamivir and prolonged corticosteroid therapy results in clinical improvement in patients with hypoxaemic respiratory failure and influenza A(H1N1), according to a study presented here at CHEST 2009, the annual meeting of the American College of Chest Physicians.
<SNIP>
By day 7 of treatment, patients had significant improvement in lung injury score (LIS) and multiple organ dysfunction syndrome as measured by the Sequential Organ Failure Assessment (SOFA) score. From day 1 to day 7, the LIS decreased from 2.83 +- 0.8 to 2.01 +- 0.5 (P = .003) in H1N1-positive patients and from 3.45 +- 0.3 to 2.15 +- 0.8 (P = .02) in H1N1-negative patients.
From day 1 to day 7, the SOFA score decreased from 5.9 +- 1.6 to 3.3 +- 2.0 (P = .01) in H1N1-positive patients and from 7.4 +- 4.1 to 3.0 +- 3.5 (P = .01) in H1N1-negative patients.
There was 1 death in the H1N1-positive patients (12.5%) thought to be due to pulmonary embolism and 1 death in the H1N1-negative group (20%) due to progression of multiple organ dysfunction syndrome.
In a related story from June of 2008, Hong Kong researchers were investigating zanamivir (Relenza) and two types of NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) used to treat lab mice infected with H5N1.
Survivability increased 4-fold with this cocktail over zanamivir alone.
The NSAIDS used were celecoxib (Celebrex) and mesalazine, an NSAID used for inflammatory bowel disease. See Research Into Antiviral/NSAID Cocktail.
# 3854
Over the July 4th weekend, Air Force Academy cadets were exposed to the H1N1 swine flu at a Barbeque and fireworks display. More than 100 developed symptoms in the 48 to 72 hours that followed.
Occurring among such a tightly monitored group, this outbreak gives us a terrific opportunity to look at the spread, treatment, and course of illness of this H1N1 virus.
Maggie Fox, ace Health and Science reporter for Reuters, brings us the details. Follow the link to read it in its entirety.
July 4 swine flu outbreak shows pattern of virus
Tue Oct 20, 2009 12:00am EDT
* Nearly one in five still have virus after getting better* Quick isolation halted spread
* Tamiflu of little help in healthy young patients
By Maggie Fox, Health and Science Editor
WASHINGTON, Oct 20 (Reuters) - More than 100 new cadets at the U.S. Air Force Academy got infected with swine flu at July 4 barbecue and fireworks display but quick isolation measures got it under control within two weeks, researchers reported on Tuesday.
The outbreak provided a unique opportunity to study the virus closely and Dr. Catherine Takacs Witkop and colleagues say they discovered some surprising things. Among them:
- Nearly a quarter, or 24 percent, of patients still had virus in their noses seven days after getting sick, including 19 percent who had been well for at least 24 hours
- Tamiflu, the drug used to treat influenza, did not help any of the previously healthy young men and women get better any quicker.
- Most cadets were sick for five days or longer
- Eleven percent of the cadets became infected.
A few things of note.
This outbreak was brought under control, according to the doctors treating the cadets, by invoking strict isolation policies.
Sick cadets were moved to a single dormitory, and remained in isolation until they were free of symptoms for 24 hours, or for 7 days after symptoms first appeared, whichever was longer.
Most cadets were sick longer than 5 days, and nasal washes showed the virus still present 24 hours after symptoms abated in nearly 20% of victims.
Whether these cadets were still infectious, absent symptoms of coughing and sneezing, is unknown.
The use of Tamiflu among healthy, fit, young cadets who experienced moderate illness (none were hospitalized, none died) showed no tangible benefit. Antivirals, it would appear, are of greatest value for those with severe symptoms.
All of which would seem to reinforce some of what we already knew.
If you get sick, STAY HOME. Don’t infect others. Remember the sage advice offered by @CarolDn (see Take The Pledge)
If you get sick, pledge to yourself: "This germ stops with me" Don't pass it forward.
That more than 10% of the attendees of this Barbeque came down with the virus within 72 hours speaks to the infectiousness of H1N1. Which is why it is so important to stay home if you are sick.
For the overwhelming majority of healthy, fit adults this virus produces a moderate, miserable, but survivable illness. But note that more than half of these cadets were sick longer than 5 days.
So if you are an employer, or a teacher, don’t be surprised if this virus causes at least a week’s absence. And that would be for uncomplicated illnesses.
As we gain more experience with this virus, we will undoubtedly see more studies of this sort, giving us a better idea of how this virus spreads, and reacts, in the population.
The health and level of fitness at the Air Force Academy, along with responsive medical care, no doubt helped to limit the impact of this virus on these cadets.
Fortunately, even in the general population, roughly 99% of those infected recover without incident.
But for the remaining 1%, H1N1 can prose a more serious threat. To those with pre-existing conditions like asthma, diabetes, and pregnancy, of course.
But even among the healthy and fit.
And right now, we don’t have a reliable way of knowing, in advance, who will do well with this virus, and who won’t.
# 3776
The `standard’ adult course of Oseltamivir (Tamiflu) for seasonal flu has long been 2 - 75mg capsules per day, for 5 days.
Or a total of 10 pills.
And despite reports from the field in countries treating the H5N1 virus that 150mg/day wasn’t terribly effective (50+% mortality rate, even with treatment), the definition of a `treatment course’ hasn’t changed.
Doctors, of course, have had the latitude to make adjustments to these regimens – and so many bird flu patients in Vietnam, China, Indonesia, and Egypt have received more than the standard 10 pill course.
In March of 2007, it was announced that doctors in Hong Kong would begin clinical trials, looking to see if higher doses of antivirals improved patient survivability. See Hong Kong: Doctors To Test Higher Tamiflu Doses.
Shortly thereafter the WHO released the following guidance which allowed for two-fold higher dosage, and longer duration on a `case by case basis’:
Accordingly, many pandemic planners (particularly in the UK) began talking about the need for more Tamiflu in their stockpile. In November of 2007, I undertook a rather long discussion of the matter in How Much Tamiflu Is Enough?
Fast forward two years, and the pandemic we’ve got isn’t the pandemic we planned for.
The H1N1 swine flu virus, thankfully, doesn’t have the high CFR (Case Fatality Ratio) of it’s avian cousin. But for a small subset of patients, the viral pneumonia it can produce easily rivals bird flu in severity.
In Hong Kong, where the H5N1 Tamiflu clinical trial was supposed to take place, one hospital has been routinely doubling the dosage of Tamiflu for their most severely ill pandemic flu patients.
And so far, at least . . . not one of them has died.
Doctors at the Prince of Wales Hospital in Hong Kong are encouraged enough by these results to recommend doubling the dose of Tamiflu for all patients who are severely impacted by the pandemic flu.
This from the Hong Kong Standard.
City flu strategy may set roadmap for global fight
Mary Ann Benitez
Monday, September 28, 2009The treatment of severely ill swine flu (H1N1) patients at Prince of Wales Hospital - which has a zero death rate so far - may be held up as a model for the world.
The World Health Organization will consider new treatment guidelines at a meeting of experts in Washington next month, and the Hong Kong model is among those being discussed.
<SNIP>
It has treated at least 60 severely ill patients, out of the city's 106 severe cases, without loss of life, according to David Hui Sui-cheong, a specialist in respiratory medicine at Chinese University.
Hui said severely ill patients should receive double the dose of Tamiflu as viral pneumonia is what kills patients with pandemic H1N1.
Antibiotics are given to patients in intensive care units to treat underlying bacterial infections brought about by long use of ventilators, he added.
