Infectious Diseases

Hey so I have some friends that have organised a charity event called Beats Not Bombs, which is happening this Friday in Swansea and they’re raising money for charity organisations called Food Not Bombs (who go on the streets and provide food to those in need) and Unity LGBT Centre (who support the LGBT homeless and vulnerable people)

I can’t actually go to the event but I’m doing commissions to help fund raise, and all money earned from this goes to charity

Bacteriophages: Antibiotic Alternative or Just a Phase?

It is now clear that we are rapidly approaching a post-antibiotic era, and the need for an alternative is more vital than ever. The CDC estimates that approximately 2 million people are infected with antibiotic resistant bacteria each year, and of that 23 000 of them die as a result of the infection [1]. Our antibiotic pipeline is drying up and the development of new antibiotics is both slow and expensive, making antibiotics unappealing investments for pharmaceutical companies. Although alternatives to antibiotics are far from the market, the field is slowly expanding. Amongst the alternatives, bacteriophages (phages) are a potential candidate for both diagnostic and therapeutic medicine.

Quite simply, phages are viruses that infect bacteria. These are the most abundant biological entity on the planet and are thought to outnumber bacteria 10:1. Their sheer abundance has led to a vast diversity that has yet to be exploited by modern medicine. This is in part due to a number of problems with phages that haven’t made them ideal candidates for therapy. This article seeks to look at some of the problems with phages, and what steps are being taken to improve them for application in humans.

Rapid clearance from the host:

Delivery systems for phages have not been thoroughly assessed for systemic phage application. In other words we are still lacking a way of delivering a bacteriophage drug intravenously to ensure that phages have the maximal effect on the patient. Annoyingly, our immune systems are great at rapidly inactivating and removing them from our bodies [2], with animal studies showing that phage can be completely cleared within 24 hours [3]. Early work carried out in germ-free mice in the 70s showed that phages are passively collected in the mononuclear phagocyte system (MPS), where they remain viable until inactivated by immune cells [3].

There have been two solutions developed so far to amend this problem [2]. The first was developed in the late 90s by the National Institute of Health in the US, which involved the serial passage of phage through a living organism. It was hypothesised that some phage would have mutations in their coat proteins that would give them increased protection from the natural filtration systems in the body over wild type phage [3] and by selecting for these phage, you could gradually produce a population of long-circulating phage. When applied, these phage would have longer circulation times, and therefore a greater chance of colliding with their target bacteria. Animal studies have shown far better recovery of animals given long-circulating strains of virus over wild type, when presenting symptoms of otherwise fatal bacteraemia [4].

Figure 1. Diagram showing a few of the possible receptors for Salmonella sp. phage [5]

Additionally, to prevent degradation or inactivation of phages, polymers can be added to the coatings of phages [1]. The polymer polyethylene glycol (PEG) has been shown to increase systematic circulation and decrease T-helper cell activation in response to phage. It is likely that a combination of these two methods may improve delivery strategies in the future of phage therapeutics.

Altering host range and preventing resistance:

Unlike antibiotics, phages have incredibly refined, narrow host-ranges. This property is in reality a double edged sword: in many cases, phages are only able to target a few strains of a single species, whereas antibiotics relentlessly target multiple branches of the bacterial phylogenetic tree. Antibiotic treatment can lead to disruption of the host’s own microbiota which can permit the colonisation of nastier and less cooperative microorganisms.

In contrast, phages can target their host whilst leaving the surrounding organisms in relative peace. When a patient presents symptoms of infection, the particular species or strain causing the infection would be unknown. Identifying the culprit before selecting the right phage would take time a patient may not have.

Receptors on the bacterial cell surface are what determine which phage are able to bind to the cell. A wide variety of receptors are used by phage, but many still remain a mystery. To curtail these issues and ensure that as many receptors can be targeted for a particular bacterium, phage cocktails are used [6]. These are mixtures containing a number of different phage strains. In theory, the cocktail should be designed so that the phages together should be able to target all the known clinically relevant strains of a particular species of bacteria.

Creating phage cocktails from natural sources can be laborious [7], however viral DNA provides a platform for genetically engineering phages with desired properties. Improving phage cocktails with modified phages expressing structures that could target a wide variety of receptors on a bacterial cell could ensure that a cocktail could target the maximum number of strains, whilst reducing the selection pressure on a sole receptor. Resistance to the phage cocktail would then also be avoided.

Much of this work looks at genetically engineering phage tail fibres [7, 8]. These ‘spider-leg’ like components regulate the initial binding step between a phage and a target cell. It has been shown by Mahichi et al, 2009 and Ando et al, 2015 that switching tail fibres between phages with different host ranges can confer host-range specificity from one phage to another. Hopefully, modular engineering of phages will push phage technology forwards, offering new strategies for developing phages for therapeutic purposes.

Figure 2. Diagram showing how the modular shuffling of tail fibres between viral strains can confer host range of parental strain [7].

Preventing the release of cellular toxins

A major health risk of phage, is that like β-lactam antibiotics, they interfere with the bacterial cell wall integrity and ultimately lead to cell lysis. Lysing cells prevents further replication, but also releases all the cell’s content. This may include but not be limited to superantigens and lipopolysaccharides (LPS) [2]. These toxins will trigger the inflammatory response, and in extreme cases cause organ failure and death.

Phages have a simple dual-lysis system consisting of a holin and endolysin. The holin is a pore-forming membrane protein that creates an exit from the cytoplasm for the endolysin. The endolysin is then able to attack the peptidoglycan of the bacterial cell wall, resulting in its rupture. To generate phage incapable of lysing a cell, the dual lysis system simply needs to be inactivated.

To restore killing power to the phage in the absense of the dual lysis system, a bacterial toxin needs to be incorporated into the phage genome. Hagens et al, 2004 has shown that by engineering the filamentous phage M13 to encode a non-native restriction enzyme, antimicrobial activity can be restored through the generation of double stranded breaks in chromosomal DNA. Upon infecting Psuedomonas aeruginosa with this phage, there was a 99% drop in viable cell counts over the time course [9]. Other research has looked into other uses for the non-lytic killing of bacteria, including proteins that interfere with regulatory systems and other bacterial toxins.

Conclusions:

Phage therapy has shown promise in recent years as being a good candidate for either working in synergy with or replacing antibiotics. The appalling lack of human based clinical trials haven’t helped to expose their potential for human use. Although this is the case, a significant amount of work has been done on improving phage therapy in preparation for further studies with human application. The past 15 years have seen an improved outcome for this technology as obstacles with phages are gradually manoeuvred by intelligent reengineering. With hindsight we have now acquired through our experiences with antibiotics, hopefully we will not make the same mistakes with phages as we have done with antibiotics.

Smart Solution To Stop Needle Reuse Wins Design Impact Award

Healthcare providers reusing unsterilized syringes and needles cause more than 1.3 million infections around the world every year, according to the World Health Organization. Ignorance of the dangers and a lack of supplies means that the average syringe is reused four times in the developing world, says advocacy and education charity Safepoint. 

The problem, which spreads bloodborne pathogens like hepatitis and AIDS HIV (h/t and good catch to sexeducationforprudes), led healthcare designer David Swann and his team at the University of Huddersfield in the United Kingdom to come up with a simple and cheap visual aid. 

They created a syringe coated with a color-changing dye that turns red when exposed to carbon dioxide. The so-called A Behavior-Changing (ABC) syringe is stored in a nitrogen-filled pack and starts changing color only when the pack is punctured or the syringe is removed. Read more below and see the video.

Biosafety Levels 1-4

We’ve known that breathing in or touching infectious/infected material is probably bad since before germ theory, but it wasn’t until 1943 that our first formal guidelines and laboratories for technician separation from the infectious agent were set up. It was the 1960s before the first conference to standardize personal protection equipment (PPE) guidelines. 

These days we have 4 basic safety levels when working with biological agents: Biosafety Levels (BSL) 1-4

BSL 1 includes well-understood agents not known to regularly affect adult humans, and which present a minimal level of hazard to the technician. Canine hepatitis, non-pathogenic strains of E. coli, and other non-infectious bacteria. Aside from standard healthy-living procedures (washing with soap etc), laboratory equipment is decontaminated via autoclave between uses, protective gloves, and sometimes protective goggles are required.

BSL 2 includes many of the milder infectious diseases that we know about, such as Salmonella, measles, mumps, MRSA, C. difficile, and hepatitis A, B, and C. These are sometimes serious illnesses, but are not easily aerosolized in a laboratory setting. When aerosols may be formed, biological safety cabinets are used, extreme care is taken with sharps, access to the laboratory is limited during work, and all technicians are trained in pathogen handling procedures.

BSL 3 includes dangerous pathogens that can cause potentially lethal infection, such as Yersinia pestis (black plague), rabies, SARS, tuberculosis, tularemia, and yellow fever. Laboratory personnel have specific training in handling pathogenic and potentially lethal agents, and are supervised by competent scientists who are experienced in working with these agents. All procedures involving the manipulation of infectious materials are conducted within biological safety cabinets, specially designed hoods, or other physical containment devices, or by personnel wearing appropriate personal protective clothing and equipment. The laboratory usually has special engineering and design features, such as restricted access, double-door entrances, and sealed penetrations. BSL 3 laboratories are sometimes called warm zones.

BSL 4 includes the most lethal and exotic agents that there are no cures or vaccines for, such as Ebola, Lassa, Argentinian hemorrhagic virus, and smallpox (smallpox for its extreme virulence, despite its vaccine availability). When dealing with biological hazards at this level the use of a positive pressure personnel suit, with a segregated air supply, is mandatory. The entrance and exit of a level four biolab will contain multiple showers, a vacuum room, an ultraviolet light room, and other safety precautions designed to destroy all traces of the biohazard. Multiple airlocks are employed and are electronically secured to prevent both doors opening at the same time. All air and water service going to and coming from a biosafety level 4 (or P4) lab will undergo similar decontamination procedures to eliminate the possibility of an accidental release. Agents with a close or identical antigenic relationship to biosafety level 4 agents are handled at this level until sufficient data is obtained either to confirm continued work at this level, or to work with them at a lower level.

Members of the laboratory staff have specific and thorough training in handling extremely hazardous infectious agents and they understand the primary and secondary containment functions of the standard and special practices, the containment equipment, and the laboratory design characteristics. They are supervised by qualified scientists who are trained and experienced in working with these agents. Access to the laboratory is strictly controlled by the laboratory director.

The facility is either in a separate building or in a controlled area within a building, which is completely isolated from all other areas of the building. A specific facility operations manual is prepared or adopted. Building protocols for preventing contamination often use negatively pressurized facilities, which, even if compromised, would severely inhibit an outbreak of aerosol pathogens.

Trans women of color with HIV may lose an important lifeline under Trump’s 2018 budget

Trans women of color living with HIV face a new challenge under Trump’s proposed 2018 budget.

Trump’s proposed budget keeps allotted funding for much of the United States-focused Ryan White Care program, which provides treatment and support services for HIV-positive Americans. 

However, it also seeks to eliminate $25 million in funding for a line item called “Special Projects of National Significance.” Part of that line item includes a $3.2 million initiative meant to keep HIV-positive transgender women of color in care.

The grant is divided among nine recipients across the United States, including the Community Healthcare Network, based in New York. 

According to Freddy Molano, the vice president of infectious diseases and LGBTQ programs, about 300 HIV-positive transgender women of color access care through CHC’s transgender care program. Read more (5/24/17)

Anti-vaxxers “targeted” Minnesota’s Somali community. Now there’s a measles outbreak.

Minnesota’s Hennepin County is in the midst of the state’s largest measles outbreak since 2011. Nine cases have been reported since last week, and officials expect the number to rise.

So far, all of the cases are among unvaccinated children. They have something else in common too: The affected children are all part of Minneapolis and St. Paul’s Somali-American community.

According to a health department official, Minnesota’s Somali immigrant community has been a particular target of the anti-vaccination movement, colloquially known as “anti-vaxxers.”

“They’re very much engaged with and targeting this community,” Kris Ehresmann, infectious disease division director at the Minnesota Health Department, said in a phone call Wednesday.

According to Ehresmann, anti-vaccine groups began to target the Somali community around 2008, amid concerns about autism among Somali-American children.

Anti-vaccine groups started reaching out to the Somali community and showing up at community health meetings, she said, disseminating misinformation linking autism to the measles, mumps and rubella vaccine, or MMR. Since then, the population has seen a “steady decline in MMR vaccine rates.” Read more (4/19/17)

Women With Microscopes

So you’ve got a half-cat, half human hybrid made in a secret laboratory. Or a race of tiger-people in the jungle outskirts. Or a race of cats that evolved a human shape on a spaceship over the last three million years.

Whether human-cat hybrids, sapient cats or anything in between, felines of many varieties suffer ailments that differ from our familiar human population. These are a few of the more notable ones that may be useful in fiction writing.

Feline Immunodeficiency Virus (FIV) is the viral agent that causes Feline Aids. The virus does more or less what it says on the tin; it causes an immunodeficiency similar to HIV in humans. It is from a different viral family than HIV though, which is why there is a vaccine available for FIV. However, the vaccine for FIV works by creating high levels of circulating antibodies, which means the vaccine must be boosted every 12 months to remain effective. It is spread as you would expect with sexual contact, but also via saliva coated penetrating wounds typical of cat bites. Cats are a fairly bitey species at the best of times. It’s worth noting that this virus can also cause lymphoma and leukemias. Domestic cats and bit cats like lions can all be infected by this virus.

Feline Leukemia Virus is a similar virus that can also cause lymphoma and leukemia. It is also spread by saliva, a particular issue for a species that mutually grooms. Some cats will only be transiently infected before ridding themselves of the virus. Others may incubate the virus for months or years before succumbing.

Cat flu is the most common disease of domestic cats kept in large groups. Technically it’s not one disease, but a combination of herpesvirus, calicivirus, and chamydia bacteria. This combination of diseases causes very sick cats with an awful combination of supprative conjunctivitis, eye ulcers, mouth ulcers and snot. Unsurprisingly the young and the old are worse affected by this and the inappetance it inevitably causes. Herpesvirus in particular is never really gone and may resurface in times of stress or leave the feline with chronic eye issues.

Ear mites are a common, easily transmitted parasite specific to cat ears. If your character just happens to have kitty ears on that otherwise humanoid head, they may well be prone to these parasites. They’re very easy to catch, live in the ear canal and are intensely itchy. Sometimes they look like moving dandruff.

Feline Panleukopenia is another nasty, highly infectious viral infection of cats. It basically attacks stem cells, mostly affecting the bone marrow (causing immunosuppresion) and sometimes diarrhoea. It’s caused by a parvovirus and is common in unvaccinated kittens. By contrast, human parvovirus causes a skin rash and mild stomach upset. In a hybrid species, who knows which parvovirus will be causing trouble.

Toxoplasma is a single celled parasite that infects both humans and felines. I’ve written a little about it in terms of a zombie apocalypse, but it is a fascinating pathogen that causes different symptoms in different species. In an intermediate host, like a mouse, sheep, kangaroo or human, the parasite forms cysts in tissues awaiting a feline to come eat the current host. In the intestines of the feline host, Toxoplasma reproduces and has a merry old time. Generally speaking the symptoms of toxoplasa in the intermediate host (the one expected to be eaten) are more severe than in the feline. These symptoms may include muscle pain, fever, neurological issues, blindness or even birth defects and abortion. By contrast, infected cats usually have little more than a fever and some diarrhoea. Interestingly you can sometimes see either set of symptoms in felines, so a humanoid feline could show any range of symptoms associated with toxoplasma.

Outdated… I’ve should have checked the expiration date. Truly, not a bad book on the subject all though I expected a bit more dept. Go to Amazon

Outdated, maybe okay for young students I studied biology in college, and took elective courses in Virology and Parasitology, and am now in a microbiology PhD program. My husband and I decided to use this edition for a community book group discussion, at the recommendation of a high school biology teacher who uses the book in his course. Go to Amazon

Scary but true If you are fascinated by medical facts and “it could happen” fiction, you’ll love this! I found it to be scary in the delicious shivery way a thriller or horror movie is, but the scariest part is that it is ALL true. It’s divided by type - bacteria, virus, parasites, fungus. Some of the things you will learn will have you staring at the book in fascinated horror. I really recommend it to medical book junkies like me :) I will just say one thing more - I will never, never, ever, ever eat raw sushi again. That section makes getting a tapeworm from sushi, as everyone talks about, seem like a mere inconvenience ~shudder~ Go to Amazon

One of the best books on the subject This was not just one of the best books I have read, but such a good book on the subject. The authors made the difficult subject of diseases and biology readily accessible, putting the topics in layman’s terms. I have enough of a background in biological sciences to understand the subject, but this was not just a dense book, it was well-written. I like the historical background of famous scientists, the connections among various diseases, vaccines, treatments, etc. This was just a great book overall that I would recommend for anyone! Go to Amazon

Great book, just needs updating I found this to be Avery informative and interesting book about all kinds of germs. My only complaint is that it has not been updated since 2003, which is a pity based upon all of the developments in this field since then. Go to Amazon

Good to Know Excellent information! I thought I knew about the subject, but I understood much more after reading this book. Given the interconnected global world we live in we all need to be aware of how viruses work and why it’s important to be cautious when using antibiotics. Go to Amazon

Such an interesting read This book is a wonderful and at times outright scary look at all those nasty germs and organisms that can kill us. The author has set the chapters out in a logical and easy to read manner. Having a very poor understanding on this subject matter I found the information easy to take in. A great mix of history, scientific facts and scenarios made this book a joy to read. This is kind of book that I know I will bore the hell out of my friends with the new knowledge it has gave me. The world of disease now lays open to me and I plan to read much more about it. Go to Amazon

Great Book! Concepts & historical perspectives explained with great clarity! This was a great book! I particularly enjoyed the historical perspectives regarding the foundations of microbiology. The chapters are organized in a very coherent and logical manner. Whether a layman or familiar with the subject, you will enjoy reading this book tremendously. I read this book on my kindle and found myself making continuous highlights on numerous quotes and analogies, which I found remarkably interesting. I would recommend this book to anyone from high school and up. Oh and this is the first time I am actually writing a review so imagine how impressed I was. Go to Amazon

How Many Times Have Viruses Almost Destroyed Humanity?

Human beings are fragile and viruses are one of the main causes for concern but what are some of the worst viruses in recorded history?