Staph Risk Runs in Families, Especially Among Siblings

Having a first-degree relative, especially a sibling, with a history of staph infection significantly increases a person’s risk for the disease, regardless of sex of the family member, co-morbid conditions, or direct contamination. The results of a large national study are published in Annals of Internal Medicine.

The incidence of Staphylococcus aureus bacteremia, or staph infection, has increased over the past few decades, with antibiotic resistance adding to the problem. Animal studies have shown a link between host genetics and staph infection, but whether human host genetics in general are associated with the risk for acquiring staph infection is unclear. This knowledge could have important implications for influencing future therapeutic interventions and strategies.

Researchers reviewed a national registry in Denmark to determine whether a history of S. aureus bacteremia in first-degree relatives is associated with an increased risk for microbiologically confirmed S. aureus bacteremia. They found that having a first-degree relative hospitalized with confirmed staph infection significantly increased a person’s risk for the disease. The risk was significantly higher if the infected patient was a sibling than a parent. According to the researchers, the results are unlikely to be explained by direct transmission of the pathogen because more than 80 percent of exposed individuals acquiring staph were infected with a strain genetically different from the infected relative.

Source: American College of Physicians

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Anthrax Capsule Vaccine Shown to Protect Against Lethal Inhalational Anthrax in Primate Model

Vaccination with the anthrax capsule–a naturally occurring component of the bacterium that causes the disease–completely protected monkeys from lethal anthrax infection, according to a study published online this week in the journal VACCINE. These results indicate that anthrax capsule is a highly effective vaccine component that should be considered for incorporation in future generation anthrax vaccines.

Bacillus anthracis, the bacterium that causes anthrax, is recognized as one of the most significant bioterrorism threats. It produces three main components that allow it to cause disease–lethal toxin, edema toxin, and capsule. During anthrax infection, the bacterium invades and grows to high concentrations in the host. The capsule surrounds the bacterium and prevents it from being ingested and destroyed by the white blood cells, thus allowing anthrax infection to progress. The toxins are thought to act mainly by damaging the body’s natural defense mechanisms.

Current human vaccines for anthrax are based on the protective antigen component of the anthrax toxins. Scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) have extensively studied protective antigen, demonstrating that protective antigen alone confers protection in animal challenge studies with both rabbits and monkeys.

However, according to senior author Arthur M. Friedlander, MD, of USAMRIID, concerns about reliance on a single antigen–as well as the issue of protecting against anthrax strains that may be vaccine resistant–have prompted the search for additional vaccine components. Bacterial capsules are commonly used in licensed vaccines for other diseases, including certain types of pneumonia and meningitis.

Friedlander’s group had already demonstrated in published studies that the anthrax capsule plays a role in conferring protection. In their current work, the team describes testing a higher dose of the capsule vaccine in monkeys against a lethal aerosol challenge with anthrax spores. All the animals receiving the capsule vaccine survived while all non-vaccinated animals succumbed to the disease.

“In the 140-year history of research on anthrax there have been two previous types of vaccine, the last one licensed in 1970,” Friedlander said. “This new capsule vaccine is expected to work against possible vaccine-resistant strains of anthrax and to protect individuals who may not respond optimally to protective antigen alone. In addition, it could be combined with protective antigen to create a multi-component vaccine that may enhance the efficacy of protective antigen- based vaccines.”

Source: U.S. Army Medical Research Institute of Infectious Diseases

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Alpaca-Derived Antibodies Point to Targets Preventing Viral Infection

Whitehead Institute scientists have determined how to use alpaca-derived, single-domain antibody fragments (also called VHHs or nanobodies) to perturb cellular processes in mammalian cells, including the infection of human cells by influenza A virus (IAV) and vesicular stomatitis virus (VSV). With improved knowledge of protein activity, scientists can tease apart the roles individual proteins play in cellular pathways, understand how disease corrupts cellular function, and begin to design interventions to rectify such aberrations.

Until now, researchers have relied largely on genetic approaches or small molecules to inhibit protein function. However, these methods’ usefulness has limits–genetic alterations may cause unintended phenotypes. Only about 15% of proteins are “druggable” using small molecules.

“Our method is an interesting and, in my opinion, an important addition to the toolbox of the molecular biologist,” says Whitehead Member Hidde Ploegh, who is also a Professor of biology at Massachusetts Institute of Technology and an affiliate member of the Koch Institute for Integrative Cancer Research at MIT. “The approach allows you to work in a wild-type protein environment–you don’t tinker with the host’s protein structure or the genetic makeup of the cell you wish to study, but rather you add a highly specific perturbant.”

Ploegh’s lab has devised a screening strategy that employs VHHs or nanobodies. These molecules are small, highly specific in what they recognize, and sturdy enough to function in the environment of the cytosol. In earlier work, the Ploegh lab used nanobodies to image the immune system’s function in real-time. Working with Whitehead Fellow Sebastian Lourido’s lab, VHHs made by the Ploegh lab helped decipher the mode of action of a key enzyme used by the Toxoplasma gondii parasite to invade cells.

In the current line of research, described online in the journal Nature Microbiology, scientists led by postdoctoral researcher Florian Schmidt have developed a rational screening approach that led to the identification of nanobodies that interfere with the ability of IAV and VSV to infect cells.

First, the scientists created nanobodies against IAV or VSV by injecting alpacas with inactivated viruses. Millions of DNA sequences, amplified from the immunized alpacas, were inserted into lentiviruses to enable expression of VHHs in the cytosol of human cells. The transduced human cells were then challenged with IAV or VSV. Any surviving cells must have produced a VHH that interferes with virus replication. Indeed, of the millions of cells transduced, about 260 contained nanobodies that protected the cells against either virus and reduced viral infection by more than 80%. When Schmidt analyzed these hits, he found that the nanobodies jammed the viruses’ infection machinery using tactics specific to each virus–anti-IAV VHHs targeted the viral nucleoprotein NP, while the anti-VSVs recognized the viral nucleocaspid N.

Using a similar, nanobody-based method, Schmidt determined the role of the adaptor protein ASC in inflammasome assembly in myeloid cells, but he envisions even broader applications for such screens.

“This technique is a very rapid way of identifying inhibitors of essentially any biological process,” he says. “And it allows us to look at all the surfaces of a collection of proteins that we’re interested in and find the sites that are important for protein function.”

By stabilizing their target molecules, nanobodies act as crystallization chaperones, which allow scientists to more easily solve the proteins’ structure. The sites where VHHs bind to proteins are also potential drug targets, as these locations impair the proteins’ activity.

This work was supported by the National Institutes of Health, Fujifilm/MediVector, and the Swiss National Science Foundation (SNSF).

Hidde Ploegh’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Professor of biology at Massachusetts Institute of Technology and an affiliate member of the Koch Institute for Integrative Cancer Research at MIT.
Reference: Schmidt FI, et al. Phenotypic lentivirus screens to identify functional single domain antibodies. Nature Microbiology, online June 20, 2016.

Source: Whitehead Institute for Biomedical Research

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How to Diagnose Systemic Infections Much More Quickly and Reliably

To date, there are no methods that can quickly and accurately detect pathogens in blood to allow the diagnosis of systemic bloodstream infections that can lead to life-threatening sepsis. The standard of care for detecting such blood-borne infections is blood culture, but this takes days to complete, only identifies pathogens in less than 30 percent of patients with fulminant infections, and it is not able to detect toxic fragments of dead pathogens that also drive the exaggerated inflammatory reactions leading to sepsis.

Biomarkers that report elevated inflammation are used clinically in the treatment of patients with sepsis; however, they fail to distinguish inflammation triggered by infectious pathogens from that induced by non-infectious causes, such as burns, traumas and surgeries.

Now, a Wyss Institute team led by Donald Ingber reports in eBioMedicine that it has filled this void with a rapid and specific diagnostic assay that could help physicians decide within an hour whether a patient has a systemic infection and should be hospitalized for aggressive intervention therapy. The potential of this assay to detect pathogen materials was demonstrated in both animal studies and a prospective human clinical study, whose results also suggest that it also could serve as a companion diagnostic to monitor the success of antibiotic and dialysis-like sepsis therapies.

“Our pathogen detection technology solves both dilemmas: it quickly reports whether infectious pathogens are present in the body, even at early stages of infection before sepsis develops. And it can more specifically identify patients who have excessive inflammation due to systemic infection, rather than other causes,” said Donald Ingber, MD, PhD, the Wyss Institute’s founding director, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. “This assay could become a real game changer in this clinical area, and it also should lead to more judicious use of antibiotics, helping to decrease the worrisome rise we are seeing in antibiotic-resistant organisms.”

“In a cohort of emergency room patients with suspected sepsis, we saw that the assay picked up infection within an hour in 85 percent of patients who exhibited clinical symptoms of sepsis, and equally importantly, it did not falsely predict infection in healthy subjects or patients with inflammation triggered by other causes, such as trauma. On the other hand, blood cultures that we performed in parallel using the same samples only detected pathogens in 18% of the cases,” said Nathan Shapiro, MD, PhD, director of translational research in the Center for Vascular Biology Research at BIDMC, who worked with Ingber’s team to conduct the clinical study. “This highlights the advance this technology represents.”

The diagnostic assay is built on FcMBL, a genetically engineered pathogen-binding protein previously developed by Ingber and Michael Super, a Wyss Senior Staff Scientist who co-leads the Institute’s pathogen-detecting effort. FcMBL binds to pathogens and pathogen-released fragments, known as Pathogen-Associated Molecular Patterns (PAMPs) by recognizing carbohydrate molecules on their surface.

Previous efforts in Ingber’s team at the Wyss Institute have established FcMBL as a key component of an advanced dialysis-like, pathogen-extracting therapeutic device, and of a method for the fast retrieval of infectious pathogens from complex clinical samples to enable their identification and antibody susceptibilities.

“In our latest work, we show that the FcMBL-based pathogen-detecting assay is considerably faster and more accurate than any other available assay for systemic infection. We are currently working to ready it for high-throughput use in clinical and point of care situations and to accelerate it even further,” said Mark Cartwright, PhD, a staff scientist at the Wyss Institute and a lead-author on the study.

As a prerequisite to their clinical study, the Wyss Institute’s team had successfully tested the assay in rat and pig models of infection with pathogenic E. coli bacteria.

“The animal models clearly told us that the assay can sensitively trace spikes of PAMPs released during antibiotic therapy, or residual infectious PAMP materials, even when no living bacteria circulate anymore in blood but they remain hidden inside internal organs. Thus, this assay could be an excellent tool for monitoring ongoing infection and responses to antibiotics and dialysis-like therapies for severe infections and sepsis,” said Mike Super, PhD.

Together, the findings suggest that the FcMBL-based pathogen detection technology with its rapid handling time, high sensitivity and broad specificity towards infection-causing pathogens could provide a real-world advance to diagnose life-threatening infections in both clinical microbiology laboratories and point-of-care settings.

The work was funded by the Wyss Institute and the Defense Advanced Research Project Agency (DARPA).

Source: Wyss Institute for Biologically Inspired Engineering at Harvard

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Angina Drug Could Inform a New Strategy to Fight Cryptococcosis

A drug more commonly used in the treatment of angina could be the focus of a new strategy in fighting the fatal fungal infection cryptococcosis. Researchers from the University of Birmingham found that the compound fendiline hydrochloride could be used to stimulate a patient’s own white blood cells to fight the disease more effectively, instead of trying to use drugs that directly kill the fungus itself.

The findings, published in the International Journal of Antimicrobial Agents, propose a role for calcium-channel blockers such as fendiline hydrochloride as potential inhibitors to the survival of Cryptococcus neoformans, the pathogen which causes cryptococcosis, and represent a promising strategy for future anticryptococcal drug design and therapy.

Professor Robin May, from the University of Birmingham, explained, “Fungi are intrinsically more difficult to target than bacteria, because they are much more closely related, evolutionarily, to humans. Finding an essential pathway in a fungus that you could inhibit, which doesn’t exist in humans, is very difficult. Therefore the approach of stimulating your own immune system to kill the fungus, instead of killing it directly through treatment, is potentially more powerful.”

In order to cause disease, Cryptococcus neoformans hides inside the patient’s own white blood cells, making it particularly difficult to treat. In the Birmingham Drug Discovery facility, the team screened 1,200 off-patent, FDA-approved, drugs to identify candidates that might be redeployed to fight cryptococcosis by triggering the white blood cells to recognize that they are infected and to kill the fungus hiding inside them.

After initial screening, 19 of those compounds in the Prestwick Chemical Library® of FDA-approved small molecules showed promise for significantly reducing intracellular growth of the pathogen.

Secondary screening and host cell toxicity assays ruled out many of these molecules, but highlighted fendiline hydrochloride, more commonly used in the treatment of angina and chest pain, as a potential candidate for the development of future anti-cryptococcal therapies.

May said, “Although calcium channel blockers have not previously been identified as a potential anticryptococcal agent, their ability to work in this way makes sense. We have previously shown that Cryptococcus perturbs calcium signaling when living inside human cells, probably in order to trick the cell into not killing it. Consequently, it’s possible that fendiline hydrochloride works by overcoming this perturbation and restoring normal calcium dynamics, helping the host to kill the fungus.

Cryptococcosis neoformans poses a major threat to immuno-compromised patients and is a leading killer of HIV patients worldwide.

HIV/AIDS patients are particularly prone to cryptococcal infections, with an estimated overwhelming disease burden of about one million cases of cryptococcal meningitis per year. The highest incidence of cryptococcal meningitis related deaths in HIV-positive patients occurs in sub-Saharan Africa with an associated mortality of 70 percent.

The infection process begins with inhalation of infectious agents (spores or dessicated yeasts) resulting in a primary pulmonary infection, which can further disseminate to the central nervous system causing meningitis.

Cryptococci are particularly difficult to treat with antifungal agents due to their ability to manipulate and exist within the host’s immune response.

Dr. Rebecca Hall, also from the University of Birmingham, added, “Considering the poor status of current anti-cryptococcal drugs, new treatment options for cryptococcosis are much needed.”

“Though the relatively high dose of fendiline hydrochloride required renders it unfit for clinical deployment against cryptococcosis in itself, our study presents an opportunity to approach treatment of this much neglected disease in a new way.”

The team note that further research is required to identify if other compounds that target calcium dynamics could be used in the fight against a much neglected disease.

This work was supported by funding from the Medical Research Council (MR/J008176/1) and the European Research Council under the European Union’s Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement No. 614562.

Source: University of Birmingham

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WHO doubles Zika sexual abstinence wait to 8 weeks before trying to conceive

Caio Julio Vasconcelos who was born with microcephaly, an abnormally small head, is kissed by a therapist at the Institute for the Blind in Joao Pessoa, Brazil, in February. (Andre Penner/Associated Press)

The UN health agency says sexual transmission of Zika is more common than first thought, so its updated advice to women who have been in areas hit by the virus tells them to wait even longer to conceive.

The World Health Organization said Tuesday that couples or women planning pregnancy who live in or are returning from Zika-hit areas “are strongly recommended to wait at least eight weeks before trying to conceive” to ensure the virus has cleared their bodies.

Previously, WHO recommended a four-week minimum period before trying to conceive in such circumstances.

If the male partner in a couple planning pregnancy has symptoms of the Zika virus, the period of safe abstinence should be six months, spokesman Christian Lindmeier told a news briefing.

The symptoms include rash, fever, arthralgia (pain in a joint), myalgia (muscle pain) or conjunctivitis.

“The new guidelines reflect what we have learned about Zika disease and its complications,” Lindmeier said.

The current outbreak of Zika has been linked to microcephaly, a rare defect in which babies are born with abnormally small heads and brain damage, and an unusual paralyzing condition known as Guillain-Barré syndrome.

Asked if this new advice amounted to an effective ban on pregnancies in Brazil, where the virus first appeared a year
ago, Lindmeier said: “The guidance is to delay or consider delaying pregnancy, certainly recognizing that this is tough for some populations.”

Sexual transmission documented in men with symptoms

The spokesman said scientists are still investigating how long the virus can be traced in saliva but these tests have so
far been inconclusive.

“All this is being studied to see where else we find the virus and how long it sustains there,” he said.

WHO said safer sexual practices include:

  • Postponing sexual debut.
  • Non-penetrative sex.
  • Correct and consistent use of male or female condoms.
  • Reducing the number of sexual partners.

So far, all published cases of sexual transmission have been from symptomatic males, whose sexual activities may have occurred before, during or after Zika symptom onset, to their partners. It remains unknown if women or asymptomatic men can transmit the virus through sexual activity, WHO said.

Zika is a mosquito-transmitted virus that generally causes mild symptoms, but is associated with microcephaly in infants whose mothers contracted the virus during pregnancy.

The Public Health Agency of Canada advises pregnant women and women considering becoming pregnant to take precautions against mosquito bites if travelling to Zika-affected countries cannot be postponed.

There have been no confirmed cases of locally acquired Zika virus through mosquitoes in Canada.

With files from Reuters and CBC News
Source: WHO doubles Zika sexual abstinence wait to 8 weeks before trying to conceive

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Yellow Fever Epidemic Threatens to Spread from Angola to China

This map shows the distribution of Aedes aegypti across Africa and the Asia-Pacific region (areas shaded pink). The red outline delineates yellow fever-endemic regions. Yellow dots represent the location of yellow fever cases related to the Angolan outbreak (source: HealthMap). Commercial flight routes with direct connections between Luanda and Beijing and indirect connections from Luanda to South and Southeast Asia via Dubai (source: FLIRT) are also represented. Courtesy of International Journal of Infectious Diseases

The spread of yellow fever (YF) is a global health threat. In response to current outbreaks in Angola, other African countries, and China, which represents the first ever documented cases of YF in Asia, the World Health Organization (WHO) convened an emergency committee on May 19, 2016 to underscore the severity of the outbreak. In the current issue of the International Journal of Infectious Diseases, noted infectious disease authorities from South Africa and Singapore explain the epidemiology and ecology of YF and discuss the factors that can increase and decrease the likelihood of progression from outbreak to epidemic.

While the YF vaccine is very effective, the WHO is concerned that the outbreak in un-vaccinated populations poses a strong risk of epidemics both in Asia and Africa. However, despite repeated references to the limited supply of vaccine, WHO did not declare the present outbreak “a global health emergency,” because the outbreak appears to be coming under control, and did not recommend lowering the dose of vaccine to extend the supply.

Unfortunately, this is a misapprehension of the actual situation. As of May 19, 2016, Angola has reported 2420 suspected cases of YF with 298 deaths (WHO Situation Report Yellow Fever 20 May 2016). Among those cases, 736 have been laboratory confirmed. Despite vaccination campaigns in Luanda, Huambo, and Benguela provinces, circulation of the virus in some districts persists. As long ago as February, a WHO expert, after visiting the country, reported that the true figures could be actually10-50 times more, meaning many thousands of cases and hundreds of deaths.

In most of the world YF is the subject of history books. Responsible for tens of thousands of deaths, the last recorded outbreak in Europe was in 1905 in Gibraltar and in the United States in New Orleans the same year. While YF traveled slowly around the world by ship in the past, it can now move quickly by air, infecting un-vaccinated populations overnight. With this increasing risk, the world’s annual vaccine production of just over 40 million doses is not nearly sufficient to replenish emergency stockpiles and contain outbreaks if YF follows the same path as dengue, chikungunya, and Zika, also spread by Aedes mosquitoes. Historically, market forces have always kept the YF vaccine supply below demand.

“The current scenario of a YF outbreak in Angola, where there is a large Chinese workforce, most of whom are un-vaccinated, coupled with high volumes of air travel to an environment conducive to transmission in Asia, is unprecedented in history,” warns lead author Sean Wasserman, MBChB, of the University of Cape Town, Cape Town, South Africa. “These conditions raise the alarming possibility of a YF epidemic, with a case fatality of up to 50 percent, in a region with a susceptible population of two billion people and where there is extremely limited infrastructure to respond effectively.”

The growing number of imported cases in China shows how critical it is to recognize this risk now in order to take adequate preemptive action so that a global catastrophe can be averted.

Epidemic YF in the Americas was successfully controlled through mass vaccination and mosquito reduction programs. Failure to sustain vector control and vaccination programs has led to the re-invasion of A. aegypti across large swaths of the Americas, as evidenced by ongoing chikungunya and Zika outbreaks. “If sufficient YF cases occur in cities to facilitate urban transmission, we may yet see YF epidemics again in the Americas,” cautions Dr. Wasserman.”

In an accompanying editorial, J.P. Woodall, PhD, from ProMED, International Society for Infectious Diseases, and T.M. Yuill, PhD, from the University of Wisconsin-Madison, emphasize that the Angola outbreak could result in the spread of YF outside of both Africa and China and that WHO alone may not have sufficient resources to contain the infection. They suggest that the United Nations may have the necessary funds and can call in multiple relief agencies to attack the epidemic.

They explain that that mosquito control alone has not been successful for stopping dengue fever and outbreaks in the tropics of Zika, another virus carried by A. aegypti. They also have little confidence in border controls being effective due to corruption and inefficiencies.

“In the final analysis, vaccination is the only solution, but there are concerns that the world may run out of doses,” according to Woodall and Yuill. “There could be a solution. Studies have shown that the vaccine is so potent that one fifth of a dose immunizes just as well – so an existing five-dose vial could protect 25 people. The WHO has the authority to declare temporary use of the lower dose, which would usefully expand the supply.”

Source: Elsevier Health Sciences



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Identification of Receptors in Patients That Spontaneously Control HIV Infection

A small number of patients infected by HIV spontaneously control viral replication without antiretroviral therapy and do not develop the disease. The ability of these rare patients, known as “HIV controllers”, to suppress HIV replication appears to be down to a highly effective immune response. Scientists from the Institut Pasteur and Inserm observed that CD4+ T immune cells in these patients, recruited from the ANRS CO21 CODEX cohort, were capable of recognizing tiny quantities of the virus. This highly sensitive detection is dependent on the expression of specific T cell receptors on the surface of immune cells, which target the HIV capsid protein with high affinity. The preferential expression of these receptors appears to keep the immune system on a constant state of alert, thereby enabling the patients to control HIV. These findings have been published in the Journal of Clinical Investigation.

“HIV controller” patients represent less than 0.5% of all HIV-infected patients. They are proof that in some cases the human immune system can resist the harmful effects of HIV. They are able to maintain a population of functional auxiliary CD4+ T lymphocytes, whereas in patients that have gone on to develop the disease these cells are destroyed or rendered inactive. The patients enrolled in the HIV controller study were recruited from the ANRS CO21 CODEX cohort which includes the few HIV controller patients living in France. Scientists in the team led by Lisa Chakrabarti (Viral Pathogenesis Unit at the Institut Pasteur/Inserm unit U1108), in collaboration with Olivier Lambotte from Bicêtre Hospital, used the cohort to analyze the CD4+ T cell responses of these patients at molecular level.

To trigger the antiviral immune response, the CD4+ T cells of HIV controllers are able to produce numerous cytokines in response to very low doses of HIV antigens. The study revealed that these highly sensitive responses were due to the expression of particular T cell receptors (TCRs) on the surface of the controllers’ CD4+ T cells. In comparison, these TCRs were rarely found on the CD4+ T cells of patients receiving treatment. The scientists showed in particular that the TCRs targeting Gag293, the HIV capsid’s most highly conserved peptide, frequently shared the same sequence in HIV controllers. These “public” TCRs have a strong affinity for the Gag293 peptide, when this peptide is presented at the surface of immune cells. This strong affinity interaction ensures the highly sensitive detection of infected cells in HIV controllers. Transferring these TCRs to healthy cells reproduces the properties typically associated with CD4+ T cells in HIV controllers, with highly sensitive responses and the production of multiple cytokines.

Overall, this research shows that the expression of high-affinity TCRs is linked with spontaneous control of HIV infection. Immunotherapy strategies based on transferring or boosting these TCRs could help restore effective antiviral responses in patients that have gone on to develop the disease.

This research was funded by the ANRS (France REcherche Nord & Sud Sida-HIV Hépatites), the French National Research Agency (ANR), the Institut Pasteur, the Australian Research Council (ARC) and the Australian National Health and Medical Research Council (NHMRC).

Source: Institut Pasteur


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Crisis over syphilis treatment as Canada running out of drug used to treat potentially deadly infection

With syphilis spreading in Canada at rates unseen in decades, doctors are struggling to cope with a shortage of the main drug used to treat the potentially deadly infection.

The Public Health Agency of Canada took the rare step recently of posting guidelines on how to ration Bicillin, and what alternative medications might be appropriate in some cases.

It’s the latest in a string of pharmaceutical supply crises to bedevil the health-care system in recent years, as government and industry hunt for solutions.

A national database lists more than 800 drugs in shortage, the date they might return to normal supply often unknown.

“It is very, very concerning to us to have supply of this drug run out, because we are in a period of resurgence of syphilis in many parts of Canada”

More worrisome is that every year sees a few “tier-three” shortages, where the lack of a drug actually affects people’s health, said Dr. Supriya Sharma, a Health Canada senior medical advisor.

The Bicillin case – caused by manufacturing problems at Canada’s sole supplier, a Pfizer plant in the United States – is one of those.

“It is very, very concerning to us to have supply of this drug run out, because we are in a period of resurgence of syphilis in many parts of Canada,” said Dr. Ameeta Singh, an Edmonton infectious-disease specialist and national syphilis expert.

“It’s actually a really big deal,” agreed Dr. Lynora Saxinger, another infectious-disease specialist at the University of Alberta. “Right now, we’re really concentrating on conserving our supplies.”

Syphilis, a major killer in the 1800s, declined steadily after the Second World War period and had almost disappeared in Canada by the 1990s. But incidence began to climb again around 2001, with the per-capita rate doubling in 10 years and the number of cases now reaching more than a 3,000 a year.

Most of the transmission has been among men having sex with men, the blame going to unsafe sex and, recently, the popularity of social-media sites that bring together partners who know little about each other’s sexual history.

But women are also getting sick, and there have been several cases recently of congenital syphilis, where mothers transmit the bacteria to newborns.

Bicillin is a form of penicillin injected into the muscle and, with its long-lasting effect, usually requires only one shot to cure the patient.

The alternative is doxycycline, an oral antibiotic taken twice daily for about two weeks.

“Now our hands are tied a bit more”

The pills are not given to pregnant women because of the risk of birth defects, and patients stay contagious longer, meaning they have to avoid sex for three weeks after the course is finished. Doctors worry patients will fail to comply with the doxycycline treatment, making it more likely they will spread the bug further.

Pregnant women unable to receive Bicillin must get intravenous penicillin, administered in a hospital every four to 10 hours.

“The problematic element for me is that at a time when syphilis rates are increasing, having a more complicated treatment regime could make it harder to control,” said Dr. Vanessa Allen of Public Health Ontario. “Now our hands are tied a bit more.”

Vincent Lamoureux, a Pfizer spokesman, refused to say what caused the production problem but said the company hopes to have it resolved by July. In the meantime, Health Canada is working with Pfizer to import surplus doses from Australia, which, ironically, were made at the same U.S. factory.

The situation arose barely two months after the last tier-three shortage, involving the epilepsy drug Epival.

The shortage problem, which first came to the fore in 2010, mostly involves older, low-cost medicines, often made by just a few generic producers. Echoing the view of many experts, Sharma said reasons for the continuing hassles are complex.

They include: provinces and health authorities contracting with only one or two suppliers; a shrinking number of companies worldwide making the active ingredients; a growing reliance on countries like India and China for pharmaceutical supply; and the impact of falling generic prices.

A “multi-stakeholder” steering group organized by federal, provincial and territorial governments is trying to hammer together solutions, said Sharma.

Lamoureux said fixing the problem is certainly not just a task for industry. Governments need to do more contingency planning, and design their drug-pricing, reimbursement and purchasing systems to lessen the risk of supply glitches, said the Pfizer official.

National Post


Source: Crisis over syphilis treatment as Canada running out of drug used to treat potentially deadly infection

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Grown-ups need vaccines too

By Dr. Brian Goldman

Flu shot immunization innoculation influenza health syringe needles

Debates and discussions around booster vaccinations usually focus on infants or children. But grown-ups should be rolling up their sleeves,too. Unfortunately, far too few adults are getting booster shots.

There are several reasons why not.  Adult immunization hasn’t been on the radar screen. When we talk only about vaccines in kids, we may be sending the message that it’s not important for adults.  Some doctors don’t mention boosters to their patients.  Some health professionals don’t know which vaccines to recommend and how often.  Adults don’t get the same coordinated immunization programs that kids get.

Annual physicals used to be a good for figuring out what shots you need.  But some provinces no longer pay for them.  Do you have an up-to-date record of immunization?  It’s hard to know where to begin without one.  And let’s not forget cost. It’s easier to roll up your sleeve when the province pays.  The out of pocket cost of herpes zoster and human papillomavirus vaccines may be prohibitive.  Some adults may believe those who say vaccines are unsafe.

Everyone needs a tetanus and diphtheria booster every ten years. Adults born after 1970 who weren’t immunized need to get one shot of measles, mumps and rubella or MMR vaccine.  For whooping cough, adults 18 years and older need one dose of acelluar pertussis-containing vaccine (found in Tdap).  As for polio, most Canadians are immune, but non-immunized adults should get the full series of shots.

Healthy adults up to the age of 24 should get meningococcal vaccine and adults age 65 and up should get one for pneumococcus.  Chicken pox vaccine should be given to susceptible adults age 18 to 40.  HPV is for women and men up to the age of 26, and to those at risk of ongoing exposure age 27 and up.  The HPV vaccine recommended for women is somewhat different than the one for men.  The shingles vaccine is recommended for adults age 60 and older.

Here are the vaccines recommended by the Public Health Agency of Canada.

If you’re thinking of taking a pass on adult immunizations, considers the stakes. If there’s a local outbreak of whooping cough, you may no longer be protected even though you received the vaccine as a child. Getting your shots up to date helps protect your kids especially babies too young for vaccines.  If there’s a local outbreak of measles, and you weren’t fully immunized as a child, you might end up getting the disease.  Adults who get measles and mumps are more likely than kids to have serious complications, and to end up in hospital.  Some countries won’t let you in if you don’t have a record of completed immunizations.  If you don’t get your shots, you won’t be a good role model to your kids who have no say in the matter.  If you develop a chronic disease like heart failure or lung disease, not getting a timely immunization might mean having to be hospitalized.

How to boost adult immunization rates is a major concern among public health officials. The Public Health Agency of Canada says there are a number of encounters between health professional and patient when adult immunization can be discussed. The list should include any first time visit, especially new immigrants.  The first prenatal pregnancy visit is another good opportunity, but keep in mind that pregnant women should wait until after 26 weeks to get a dose of pertussis vaccine, and should wait until after the baby is born to get MMR.  Immunization should be discussed every time an adult is admitted to hospital or to a long-term care facility.  When parents bring their kids for immunizations, it could very effective to discuss the subject with the parents as well.

The most obvious one occurs when the patient asks for travel advice.  Every time I travel overseas, I have my vaccination record updated.  I urge you to talk to your health professional about updating your immunizations.

Source: Grown-ups need vaccines too

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