Ebola Deuxième Partie: vaccin

This is the second installment in the Ebola Hemorrhagic Fever (see part 1 here), since there seems to be a bit of misinformation circulating. This is merely a swift breakdown of current research and doesn't address political issues regarding it. It's also a quick breakdown on how exactly vaccinations work.

To quickly recap, Ebola Hemorrhagic Fever is currently causing devastation in Sierra Leone, Guinea, and Liberia. With a death toll of over a thousand and climbing, and treatment of U.S. doctors and missionaries (CNN), everyone is calling for a vaccination.

And a quick recap of how vaccinations work. The body protects itself from disease via the production of antibodies by the immune system that target foreign"antigens" (germs). The body remembers these antigens and gives a much faster response if there is a repeat infection. The immune system, however, can sometimes be too slow to respond to prevent sickness. That's where vaccines come in. Vaccinations are effective because they contain antigens that have been that have been killed or weakened to the point where they don't cause disease, but still allow antibodies to develop against them. This way if infection does occur, the body already has memory of it and can respond much faster so sickness doesn't occur.

There is a promising filovirus vaccine under development for Ebola Hemorrhagic Fever based on recombinant vesicular stomatitis virus. This type of vaccine has shown to be 100% effective against Marburg virus and 3 species of the Ebola virus in nonhuman primates. There are caveats, though; protection is only good for 28-35 days after a single injection, and this hasn't undergone human trials.

Correction from reliable sources is always appreciated.

Goodbye (to blogger)

Thank you all for your interest and support in making this blog go "viral". I hope you enjoyed reading about the dark (and gross) side of biology as much as I had writing it. But fear not (or do), things that go bump in your body will be bumping in another host. Stay tuned, stay healthy, and keep your hands clean and food thoroughly cooked.

Chiku-chiku-ngunya

Countries & territories where chikungunya
cases have been reported as of July 15th, 2014.
Does not include countries or territories with only imported cases.
Map courtesy of CDC

Since 2006, the U.S. has average 28 chikungunya (pronounced \chik-en-gun-ye) cases a year in travelers returning from countries where the disease is common, and the mosquito-borne virus was first identified in the Western Hemisphere seven months ago. But on July 17th, 2014, a man in Florida was the first to locally acquire hte disease in the continental U.S.

Transmission electron micrograph
of  numerous chikungunya virus
particles. Image courtesy of CDC

Chikungunya, a single-stranded RNA virus from the Togaviridae family, is transmitted via Aedes aegypti and Aedes albopictus mosquito bites in humans.  Most people infected with the chikungunya virus will develop symptoms-which are primarily fever and joint pain-three to seven days after being bitten by an infected mosquito.  Other symptoms include headache, muscle pain, joint swelling, or rash.  It's not often a fatal disease, but the symptoms can be severe and disabling. Most recover within a week, although the joint pain can last for months.  The highest risk groups are newborns, adults above the age of 65, and those with high blood pressure, diabetes, or heart disease.  The good news is once a person has been infected, they are likely protected from future infections.

Aedes aegypti & Aedes albopictus.  Courtesy of CDC

Courtesy of CDC

Courtesy of CDC

The course of chikungunya is unknown, but CDC officials believe it will behave like the dengue virus, where imported cases have resulted in sporadic local transmission but not widespread outbreak.  There is no vaccine or targeted treatment for the chikungunya virus. To preven infection, the use of A/C, window and door screens or mosquito bed netting, DEET/picaridin/IR3535/oil of lemon eukalyptus/para-menthane-diol products, and long-sleeved shirts and long pants.  It is also recommended to empty standing water from containers like flower pots and buckets to reduce the number of mosquitoes outside the home.  The CDC and the Florida Department of Health aremonitoring for additional cases and consulting the public on ways to prevent chikungunya from spreading.  

Anthrax-We are our own worst enemy

Figure courtesy of the CDC

Last week we talked about how vials of smallpox were found in a FDA laboratory, showing that even labs are guilty of having that old, over-crowded stockroom that's in every office complex. And here's another reminder that labs are as prone to human error and politics as any office-the CDC has released an after-action report regarding employees' exposure to anthrax. For those that are just tuning in, extracts and cultures of Bacillus anthracis (anthrax) in the Bratt BSL*-3 lab were sent to different laboratories on June 6th and June 12th with a potential for aerosolization.

Figure courtesy of CDC

This is not the first time B. anthracis has been in the news. The bacteria is a serious infectious disease that can be found naturally in soil and commonly affects domestic and wild animals. It is rare in developed nations where veterinary public health programs vaccinate livestock against it. Those few who get sick from it are infected from breathing in the spores, eating food or drinking contaminated water, or from spores in a scrape on the skin. Other members of the Bacillus genus (and there are several) can be non-pathogenic or pathogenic, but are none are as virulent as anthrax.

Photomicrograph of Bacillus anthracis using Gram-stain technique
Image courtesy of CDC

The type of illness depends on the type of anthrax. Cutaneous anthrax causes a group of small blisters or bumps that may itch and/or a painless skin sore with a black center. Inhaled anthrax spores result in fever/chills, chest discomfort, shortness of breath, confusion or dizziness, cough, nausea/vomiting/stomach pains, headache, drenching sweats, extreme tiredness, and body aches. Gastrointestinal anthrax symptoms are fever/chills, swelling of neck or neck glands, sore throat, painful swallowing, hoarseness, bloody diarrhea, headache, face flush, red eyes, stomach pain, fainting, and swelling of the abdomen. Injected anthrax is similar to cutaneous, but quicker and harder to recognize and treat.

While the incident was unfortunate, none of the staff became ill from anthrax and it triggered the development of new safety protocols. And, of course, none of it escaped the CDC.

Figure Courtesy of CDC

*BioSafety Level: the application of precautions that reduce a laboratorian's risk of exposure to infectious microbes and limit work space contamination. There are four levels, and each has specific containment controls of biological agents based on infectivity, severity, transmissibility, and work conducted.

Big things come in small poxages

On July 1st, employees at a laboratory on the National Institutes of Health Bethesda campus found vials of smallpox from the 1950s while preparing for the lab's relocation to the FDA's main campus. This laboratory had been transferred from NIH to FDA in 1972, and the FDA has operated laboratories located on the NIH campus since then. The vials themselves have since been secured in the CDC's high-containment facility in Atlanta, and are currently undergoing testing for viability. Upon completion, if the samples are viable, they will be destroyed and, as per protocol, the World Health Organization has been invited to witness. Currently, there are two WHO-designated repositories for smallpox, the CDC and the State Research Centre of Virology and Biotechnology in Novosibirsk, Russia. The CDC's Division of Select Agents and Toxins is investigating the history of how these samples were originally prepared and stored in the FDA laboratory.

Gutstein Methyl Violet stain of smallpox skin lesion.
Viral particles stain light to dark violet
Image courtesy of CDC

Smallpox is a highly contagious and sometimes fatal infectious disease that has no specific treatment, only a vaccination. There are two forms of the virus, variola major (the most severe and most common) and variola minor, both of which are only hosted in humans. Variola major is divided into four types, ordinary (the most common), modified (occurring in those previously vaccinated), flat, and hemorrhagic (both rare and very severe). Variola major has on average a fatality rate of about 30%, but the last two are usually fatal.

Smallpox vs. chickenpox
rash distribution
Image courtesy of CDC

Direct and prolonged face-to-face contact is required to spread smallpox, but can be spread through direct contact with infected body fluids or contaminated objects. Symptoms begin with an onset of fever, malaise, head, and body aches with occasional vomiting. Small red spots on the tongue and mouth then emerge, spreading to the face and the rest of the body and lastly to the feet. This rash then becomes raised bumps filled with a thick, opaque fluid with a depression in the center. The bumps then become pustules-sharply raised, round and firm, which then begin to scab and eventually fall off, leaving pitted scars. The duration of the entire disease may be several week, but the person is most contagious for the week following the rash outbreak.

The disease is now eradicated thanks to a worldwide vaccination program. The last case in the U.S. was in 1949 and the last one globally was in Somalia in 1977. Routine vaccination was discontinued after smallpox's eradication.

Go Go Gonorrhoeae

Antibiotic resistance is nothing new in the world of health care. Most deaths related to antibiotic resistant bacteria are in health care settings, such as hospitals and nursing homes. However, there is an organism that is causing concern for those outside of these environments, and that is Neisseria gonorrhoeae (also known as "the clap").

3D computer-generated image
of drug-resistant N. gonorrhoeae
Image courtesy of CDC

N. gonorrhoeae is one of several species of the genus Neisseria, which contains both normal flora and pathogens of humans and animals. N. gonorrhoeae is a common sexually transmitted disease that causes infection in the genitals, rectum, and throat, and can also be spread to an infant from an infected mother during childbirth. Symptoms of infection include a burning sensation when urinating, a yellow, green, or white discharge from the penis, and occasionally painful or swollen testicles. Most infected women are asymptomatic, and those that have symptoms are often mild and mistaken for a bladder or vaginal infection. All infected women are susceptible to serious complications, characterized by painful or burning sensation when urinating, increased vaginal discharge, and vaginal bleeding between menstrual cycles. Signs of symptomatic rectal infections are discharge, anal itching, soreness, bleeding, and painful bowel movements.

Figure Courtesy of CDC

N. gonorrhoeae is becoming a health concern because it has developed resistance to sulfonilamide, penicillin, tetracycline, and fluoroquinolone (ex. ciproflaxin) antibiotics. N. gonorrhoeae is readily able to develop resistance, which would complicate treatment, since there are few options left that are simple, well-studied, well-tolerated, and highly effective. The current recommended therapy is cephalosporin ceftriaxone plus either azithromycin or doxycycline. N. gonorrhoeae is under surveillance by the Gonococcal Isolate Surveillance Project (GISP), established in 1986.

Figure courtesy of CDC

Clinicians are asked to report any N. gonorrhoeae specimen that demonstrates decreased cephalosporin susceptibility and any cephalosporin treatment failure. Outside the U.S., ceftriaxone-resistant N. gonorrhoeae have already been reported in Japan and South Africa.

La Fièvre Hémorragique Ebola

One of the worst outbreaks of Ebola Hemorrhagic Fever (Ebola HF), a severe and often fatal disease in humans and other primates, is occurring in Guinea, Sierra Leone, and Liberia. Between the three, 338 fatal cases have occurred, with several more laboratory confirmation and reports in other districts.

Ebola Hemorrhagic Fever Distribution Map
Image Courtesy of CDC

Colorized Transmission Electron Micrograph
of Ebola Virus virion
Image courtesy of CDC

Ebola HF is a virus within the family Filoviridae, genus Ebolavirus. There are five subspecies of the Ebolavirus family, four of which cause disease in humans: Ebola virus (Zaire ebolavirus), Sudan virus (Sudan ebolavirus), Taï Forest Virus (Taï Forest ebolavirus, formerly, Côte d'Ivoire ebolavirus), and the Bundibugyo virus (Bundibugyo ebolavirus).

First discovered in the Democratic Republic of the Congo near the Ebola River in 1976, outbreaks have been sporadically occurring in endemic regions. The natural reservoir, or host, of ebolaviruses is still unknown, although native bats are strongly suspected due to the nature of similar viruses. Besides from the animal host, the virus can be transmitted between people by direct contact with the blood or secretions (i.e. urine, feces, saliva) of an infected person or exposure to contaminated objects. Those most often infected are families and friends that come in close contact while caring for the ill, or those in health care settings where appropriate protective equipment (masks, gloves, gowns, etc.) aren't worn and proper cleaning and disposal of medical instruments isn't performed.

Life Cycle of the Ebolavirus
Image courtesy of CDC

Symptoms of the virus may appear 2 to 21 days after exposure, although 8 to10 days is most common. Symptoms of those infected include fever, headache, joint and muscle aches, weakness, diarrhea, vomiting, stomach pain, and lack of appetite. Some may experience a rash, red eyes, hiccups, cough, sore throat, chest pain, difficulty breathing and swallowing, and bleeding inside and outside the body. The reasons behind why some get sick and are able to recover while others are not is not fully understood, although fatalities are usually in those who haven't developed a significant immune response to the virus at the time of death. Diagnosis of this disease is difficult because early symptoms of red eyes, skin rash, fever, and headache also occur in more common diseases, and treatment is supportive (balancing patients' fluids and electrolytes, maintaining oxygen status and blood pressure, and treating for any other complicating infections).

Ebola HF is unlikely to spread to nations outside of the African continent. The only reported instance of Ebola transmission in the US was Ebola-Reston virus (the fifth subspecies that doesn't cause disease in humans) from imported research monkeys in 1990, and it didn't result in clinically apparent disease.