Inside the Chinese lab poised to study world s most dangerous pathogens: Nature News — Comment

Inside the Chinese lab poised to study world’s most dangerous pathogens

Maximum-security biolab is part of plan to build network of BSL-4 facilities across China.

Editors’ note, January 2020: Many stories have promoted an unverified theory that the Wuhan lab discussed in this article played a role in the coronavirus outbreak that began in December 2019. Nature knows of no evidence that this is true; scientists believe the most likely source of the coronavirus to be an animal market.

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Wuhan Virology Institute

Hazard suits hang at the National Bio-safety Laboratory, Wuhan, the first lab on the Chinese mainland equipped for the highest level of biocontainment.

A laboratory in Wuhan is on the cusp of being cleared to work with the world’s most dangerous pathogens. The move is part of a plan to build between five and seven biosafety level-4 (BSL-4) labs across the Chinese mainland by 2025, and has generated much excitement, as well as some concerns.

Some scientists outside China worry about pathogens escaping, and the addition of a biological dimension to geopolitical tensions between China and other nations. But Chinese microbiologists are celebrating their entrance to the elite cadre empowered to wrestle with the world’s greatest biological threats.

“It will offer more opportunities for Chinese researchers, and our contribution on the BSL‑4-level pathogens will benefit the world,” says George Gao, director of the Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology in Beijing. There are already two BSL-4 labs in Taiwan, but the National Bio-safety Laboratory, Wuhan, would be the first on the Chinese mainland.

The lab was certified as meeting the standards and criteria of BSL-4 by the China National Accreditation Service for Conformity Assessment (CNAS) in January. The CNAS examined the lab’s infrastructure, equipment and management, says a CNAS representative, paving the way for the Ministry of Health to give its approval. A representative from the ministry says it will move slowly and cautiously; if the assessment goes smoothly, it could approve the laboratory by the end of June.

BSL-4 is the highest level of biocontainment: its criteria include filtering air and treating water and waste before they leave the laboratory, and stipulating that researchers change clothes and shower before and after using lab facilities. Such labs are often controversial. The first BSL-4 lab in Japan was built in 1981, but operated with lower-risk pathogens until 2015, when safety concerns were finally overcome.

The expansion of BSL-4-lab networks in the United States and Europe over the past 15 years — with more than a dozen now in operation or under construction in each region — also met with resistance, including questions about the need for so many facilities.

“Viruses don’t know borders.”

The Wuhan lab cost 300 million yuan (US$44 million), and to allay safety concerns it was built far above the flood plain and with the capacity to withstand a magnitude-7 earthquake, although the area has no history of strong earthquakes. It will focus on the control of emerging diseases, store purified viruses and act as a World Health Organization ‘reference laboratory’ linked to similar labs around the world. “It will be a key node in the global biosafety-lab network,” says lab director Yuan Zhiming.

The Chinese Academy of Sciences approved the construction of a BSL-4 laboratory in 2003, and the epidemic of SARS (severe acute respiratory syndrome) around the same time lent the project momentum. The lab was designed and constructed with French assistance as part of a 2004 cooperative agreement on the prevention and control of emerging infectious diseases. But the complexity of the project, China’s lack of experience, difficulty in maintaining funding and long government approval procedures meant that construction wasn’t finished until the end of 2014.

The lab’s first project will be to study the BSL-3 pathogen that causes Crimean–Congo haemorrhagic fever: a deadly tick-borne virus that affects livestock across the world, including in northwest China, and that can jump to people.

Future plans include studying the pathogen that causes SARS, which also doesn’t require a BSL-4 lab, before moving on to Ebola and the West African Lassa virus, which do. Some one million Chinese people work in Africa; the country needs to be ready for any eventuality, says Yuan. “Viruses don’t know borders.”

Gao travelled to Sierra Leone during the recent Ebola outbreak, allowing his team to report the speed with which the virus mutated into new strains 1 . The Wuhan lab will give his group a chance to study how such viruses cause disease, and to develop treatments based on antibodies and small molecules, he says.

Muyi Xiao for Nature

The central monitor room at China’s National Bio-safety Laboratory.

The opportunities for international collaboration, meanwhile, will aid the genetic analysis and epidemiology of emergent diseases. “The world is facing more new emerging viruses, and we need more contribution from China,” says Gao. In particular, the emergence of zoonotic viruses — those that jump to humans from animals, such as SARS or Ebola — is a concern, says Bruno Lina, director of the VirPath virology lab in Lyon, France.

Many staff from the Wuhan lab have been training at a BSL-4 lab in Lyon, which some scientists find reassuring. And the facility has already carried out a test-run using a low-risk virus.

But worries surround the Chinese lab, too. The SARS virus has escaped from high-level containment facilities in Beijing multiple times, notes Richard Ebright, a molecular biologist at Rutgers University in Piscataway, New Jersey. Tim Trevan, founder of CHROME Biosafety and Biosecurity Consulting in Damascus, Maryland, says that an open culture is important to keeping BSL-4 labs safe, and he questions how easy this will be in China, where society emphasizes hierarchy. “Diversity of viewpoint, flat structures where everyone feels free to speak up and openness of information are important,” he says.

Yuan says that he has worked to address this issue with staff. “We tell them the most important thing is that they report what they have or haven’t done,” he says. And the lab’s inter­national collaborations will increase openness. “Transparency is the basis of the lab,” he adds.

The plan to expand into a network heightens such concerns. One BSL-4 lab in Harbin is already awaiting accreditation; the next two are expected to be in Beijing and Kunming, the latter focused on using monkey models to study disease.

Lina says that China’s size justifies this scale, and that the opportunity to combine BSL-4 research with an abundance of research monkeys — Chinese researchers face less red tape than those in the West when it comes to research on primates — could be powerful. “If you want to test vaccines or antivirals, you need a non-human primate model,” says Lina.

But Ebright is not convinced of the need for more than one BSL-4 lab in mainland China. He suspects that the expansion there is a reaction to the networks in the United States and Europe, which he says are also unwarranted. He adds that governments will assume that such excess capacity is for the potential development of bioweapons.

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“These facilities are inherently dual use,” he says. The prospect of ramping up opportunities to inject monkeys with pathogens also worries, rather than excites, him: “They can run, they can scratch, they can bite.”

Trevan says China’s investment in a BSL-4 lab may, above all, be a way to prove to the world that the nation is competitive. “It is a big status symbol in biology,” he says, “whether it’s a need or not.”

www.nature.com

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Lyme Disease Tests

What are Lyme disease tests?

Lyme disease is an infection caused by bacteria carried by ticks. Lyme disease tests look for signs of infection in your blood or cerebrospinal fluid.

You can get Lyme disease if an infected tick bites you. Ticks can bite you anywhere on your body, but they usually bite in hard-to-see parts of your body such as the groin, scalp, and armpits. The ticks that cause Lyme disease are tiny, as small as a speck of dirt. So you may not know you have been bitten.

If left untreated, Lyme disease can cause serious health problems affecting your joints, heart, and nervous system. But if diagnosed early, most cases of Lyme disease can be cured after a few weeks of treatment with antibiotics.

Other names: Lyme antibodies detection, Borrelia burgdorferi antibodies test, Borrelia DNA Detection, IgM/IgG by Western Blot, Lyme disease test (CSF), Borrelia antibodies, IgM/IgG

What are they used for?

Lyme disease tests are used to find out if you have a Lyme disease infection.

Why do I need a Lyme disease test?

You may need a Lyme disease test if you have symptoms of infection. The first symptoms of Lyme disease usually show up between three and 30 days after the tick bite. They may include:

You may also need a Lyme disease test if you don’t have symptoms, but are at risk for infection. You may be at a higher risk if you:

  • Recently removed a tick from your body
  • Walked in a heavily wooded area, where ticks live, without covering exposed skin or wearing repellent
  • Have done either of the above activities and live in or have recently visited the northeast or midwestern areas of the United States, where most Lyme disease cases occur

Lyme disease is most treatable in its early stages, but you may still benefit from testing later on. Symptoms that may show up weeks or months after the tick bite. They may include:

  • Severe headache
  • Neck stiffness
  • Severe joint pain and swelling
  • Shooting pains, numbness, or tingling in the hands or feet
  • Memory and sleep disorders

What happens during Lyme disease testing?

Lyme disease testing is usually done with your blood or cerebrospinal fluid.

For a Lyme disease blood test:

  • A health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.

If you have symptoms of Lyme disease affecting your nervous system, such as neck stiffness and numbness in hands or feet, you may need a test of cerebrospinal fluid (CSF). CSF is a clear liquid found in your brain and spinal cord. During this test, your CSF will be collected through a procedure called a lumbar puncture, also known as a spinal tap. During the procedure:

  • You will lie on your side or sit on an exam table.
  • A health care provider will clean your back and inject an anesthetic into your skin, so you won’t feel pain during the procedure. Your provider may put a numbing cream on your back before this injection.
  • Once the area on your back is completely numb, your provider will insert a thin, hollow needle between two vertebrae in your lower spine. Vertebrae are the small backbones that make up your spine.
  • Your provider will withdraw a small amount of cerebrospinal fluid for testing. This will take about five minutes.
  • You’ll need to stay very still while the fluid is being withdrawn.
  • Your provider may ask you to lie on your back for an hour or two after the procedure. This may prevent you from getting a headache afterward.

Will I need to do anything to prepare for the test?

You don’t need any special preparations for a Lyme disease blood test.

For a lumbar puncture, you may be asked to empty your bladder and bowels before the test.

Are there any risks to Lyme disease tests?

There is very little risk to having a blood test or a lumbar puncture. If you had a blood test, you may have slight pain or bruising at the spot where the needle was put in, but most symptoms go away quickly. If you had a lumbar puncture, you may have pain or tenderness in your back where the needle was inserted. You may also get a headache after the procedure.

What do the results mean?

The Centers for Disease Control and Prevention (CDC) recommends a two-test process of your sample:

  • If your first test result is negative for Lyme disease, you don’t need any more testing.
  • If your first result is positive for Lyme disease, your blood will get a second test.
  • If both results are positive for Lyme disease and you also have symptoms of infection, you probably have Lyme disease.

Positive results don’t always mean a Lyme disease diagnosis. In some cases, you can have a positive result but not have an infection. Positive results may also mean you have an autoimmune disease, such as lupus or rheumatoid arthritis.

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If your lumbar puncture results are positive, it may mean you have Lyme disease, but you might need more tests to confirm a diagnosis.

If your health care provider thinks you have Lyme disease, he or she will prescribe antibiotic treatment. Most people who are treated with antibiotics in the early stage of disease will make a complete recovery.

Is there anything else I need to know about Lyme disease tests?

You can reduce your chances of getting Lyme disease by taking the following steps:

  • Avoid walking in wooded areas with high grass.
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  • Apply an insect repellent containing DEET to your skin and clothing.

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Structure and Function of the Gastrointestinal Tract in Dogs

Dr. Bari Spielman

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Below is information about the structure and function of the canine gastrointestinal tract. We will tell you about the general structure of the stomach and bowels, how it works in dogs, common diseases that affect the gastrointestinal tract and common diagnostic tests performed in dogs to evaluate the gastrointestinal tract.

What Is the Gastrointestinal Tract?

The gastrointestinal (GI) tract or system is responsible for processing and extracting nutrients from food and collecting and passing waste material from the dog’s body. It is a very long and winding tube, beginning in the mouth and ending at the anus, through which food is swallowed and collected, then broken apart and digested. It is also where the nutrients from food are absorbed into the body. The GI tract includes the mouth, teeth, tongue, pharynx, esophagus, stomach, small intestine and large intestine.

Where Is the Gastrointestinal Tract Located in Dogs?

The GI tract is a large system that travels the length of the body. It starts at the mouth, extends into the throat, through the chest and abdominal cavities, and ends at the anus.

  • Mouth. Food is initially grasped by the teeth and tongue and enters the mouth. As the food is swallowed, it passes into the back of the mouth, which is known as the pharynx. Both food and air pass through the pharynx on their way into the body.
  • The esophagus is the connecting tube between the pharynx and the stomach. As food leaves the pharynx it enters the esophagus and travels down the neck and through the chest. The esophagus passes through the diaphragm (the muscle that separates the chest from abdominal cavity) and ends at the stomach.
  • The stomach lies in the front of the abdominal cavity, just behind the liver. It is situated between the esophagus and the small intestine, lying predominantly on the left side of the body.
  • The small intestine is located within the abdominal cavity and extends from the stomach to the junction of the small and large intestine.
  • The cecum is a small dead-end pouch that lies near the junction of the small and large intestines. The colon begins in the lower portion of the right side of the abdomen and travels forward along the right side, then crosses the midline, and proceeds back down the left side. This last portion of the colon (descending colon) leads into the rectum and then empties through the anus. The rectum is the terminal portion of the large intestine that passes through the pelvis and leads to anus.

    What Is the General Structure of the Gastrointestinal Tract?

    For most of its length, the GI tract is a long hollow tube lined by different types of cells. The walls of the tube are composed of glands, nerves and muscles. Structurally, the cell type, muscle thickness, glandular elements, and nervous supply differ in the various functional regions, as does the diameter and shape of the tube.

  • The esophagus is a rather straight tube that is lined with muscles that force food down the neck and through the chest towards the stomach. In a medium-sized dog it is about 15 to 18 inches long and an inch in diameter when collapsed. It is divided into cervical (neck), thoracic (chest), and abdominal portions.
  • The stomach is a large sac-like dilatation of the GI track and is made up of several distinct areas. The inlet or opening from the esophagus into the stomach is called the cardia. The exit or outlet of the stomach that leads to the small intestine is the pylorus. The stomach is shaped somewhat like a large lopsided kidney bean that lies across the front of the abdomen. The left side of the stomach, closest to the cardia is larger than the right side and is called the fundus. The smaller right-sided portion of the stomach that ends at the pylorus is called the body of the stomach. The lining of the stomach contains glands that produce acids and enzymes that digest food and the walls of the stomach contain muscles that mix and move the food. The glands of the stomach also produce mucous, which protects the stomach from being digested by its own acid and enzymes.
  • The small intestine is the longest portion of the GI tract. It is a circular hollow tube that is approximately three to four times the length of the animal’s body. The interior lining of the small intestines has numerous microscopic, finger-like projections called villi. These villi stick out towards the center of the intestine and greatly increase the surface area available for digestion and absorption.

    The small intestine consists of the duodenum, the jejunum and the ileum. The duodenum is the first and most stationary part of the small intestine. Within the duodenum, openings are present that allow digestive juices to enter the intestines from the pancreas and gallbladder. The jejunum is the longest part of the small intestine and is free to move into whatever unoccupied space is available within the abdomen. The ileum is the short, terminal portion of the small intestine.

    The large intestine is wider and shorter than the small intestine. It includes the cecum, colon, rectum, and anal canal. The cecum is a comma-shaped pouch that lies at the junction of the ileum and colon. The colon is shaped like a question mark. It is thin-walled and baggier than the small intestines. The rectum is the last few inches of the colon and leads directly to the anal canal. The anal canal is the short, terminal part of the GI tract that lies just inside the anus. It is only about one-half inch in length. The anus has two muscular sphincters that act as a door, holding the stool (fecal material) inside the body until it is appropriate to defecate.

    The components of the GI tract that lie within the abdomen are held in place by their attachments to the mesentery. The mesentery is a curtain-like structure that hangs from the top of the middle of the abdomen. It contains blood vessels that travel to and from the GI tract. It also contains lymph vessels that carry certain nutrients away from the GI tract.

    What Are the Functions of the Canine Gastrointestinal Tract?

    What Are Common Diseases of the Gastrointestinal Tract in Dogs?

    There are many primary disorders that affect the GI tract. Vomiting and/or diarrhea are commonly seen with gastrointestinal disease. Regurgitation (the effortless evacuation of fluid, mucus and undigested food from the esophagus) is commonly seen with esophageal disease. Some common diseases of the GI tract include:

  • Congenital defects. They may lead to defects in swallowing or movement of food through the esophagus, inability to properly digest food, or inability to defecate.
  • Infectious agents including bacteria, viruses, fungal and protozoal organisms, as well as intestinal parasites are quite common in both cats and dogs. Different infections often involve isolated portions of the GI tract.
  • Inflammation. Various inflammations can develop any where along the GI tract. When inflammation arises in the mouth, it is called stomatitis. Inflammation of the esophagus is esophagitis. Gastritis is inflammation of the stomach. Enteritis is inflammation of the intestine. Colitis is inflammation of the colon. Inflammation of the rectum is proctitis. These types of inflammation can be either acute or chronic.
  • Inflammatory bowel disease (IBD) is a microscopic infiltration of the small intestinal wall with inflammatory cells. It is believed to be associated with an abnormal immune response to environmental stimuli that, when continued, creates a self-perpetuating inflammation resulting in the disease.
  • Intussusceptions (telescoping of part of the bowel into an adjacent segment of bowel) are seen in both cats and dogs. They are often associated with parasites, foreign bodies, tumors or chronic diarrhea, and usually affect the small intestines of young animals.
  • Foreign bodies (rocks, bits of clothing) of the GI tract are common in cats and dogs due to their indiscriminate eating habits. They result in local inflammation, obstruction and sometimes perforation of the GI tract.
  • Ulcerative gastroenteritis (interruptions in the lining of the gastrointestinal tract) may develop and be secondary to inflammation, drug administration, neoplasia or foreign bodies.
  • Hemorrhagic gastroenteritis (HGE) is a dramatic, potentially fatal disorder causing sudden onset bloody diarrhea in adult dogs. Although the exact cause is unknown, it may be due to some sort of bacterial toxin. HGE has a predilection for small breed dogs.
  • Acute gastric dilatation or bloat is a condition seen mainly in large, deep-chested breeds of dogs. For a variety of reasons, the stomach suddenly dilates like a balloon and fails to empty. It may twist upon itself (called a volvulus), and entirely obstruct the opening/exit passages of the stomach. Acute gastric dilatation is a life-threatening emergency that may rapidly result in shock and collapse of the dog.
  • Paralysis of portions of the GI tract may occur. Paralysis of the esophagus results in a grossly enlarged esophagus, known as megaesophagus, and regurgitation of food and water. Paralysis of the stomach results in delayed gastric emptying. Paralysis of the intestines is known as ileus. Paralysis of the colon results in enlargement of the colon (megacolon) and constipation.
  • Certain abnormalities in the digestion and absorption of nutrients can occur, particularly in the small intestines. These are known as maldigestion and malabsorption disorders. Diseases can also arise that result in the excessive loss of nutrients into the intestines, which then pass out of the body through the feces.
  • Trauma can occur along different segments of the GI tract. Trauma to the esophagus most often arises with bite wounds to the neck. The intestines may be injured through either blunt abdominal trauma (e.g. automobile accidents, falling from heights, kicking injuries) or penetrating trauma (e.g. bite wounds, bullet and arrow wounds, falling on sharp objects). Trauma to the pelvis and tail may affect the rectum and anal canal.
  • Tumors may develop anywhere along the entire length of the intestinal tract. Different tumors arise in different areas because the types of cells present in each area are unique. Tumors of the gastrointestinal tract may be either benign or malignant. They can grow into the cavity of the tract, and can involve the wall of the tract or the surrounding soft tissues.

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    What Types of Diagnostic Tests Are Used to Evaluate the Gastrointestinal Tract?

    Numerous diagnostic tests are helpful in evaluating the GI tract.

  • Baseline tests such as a complete blood count (CBC), biochemical profile, and urinalysis are essential, as changes in these tests may suggest infection, inflammation, electrolyte and acid-base imbalances, and/or other organ involvement.
  • Serologic tests for viruses, fungi, protozoal and tick borne infections may be indicated. Measurement of certain circulating nutrients in the body (Vitamin B, folate, etc.) may be done to assess the absorption capabilities of the intestines. Specialized tests that look for ingestion and exposure to toxins, such as lead and botulism, may be helpful. Certain immune tests are indicated when immune-mediated diseases are suspected.
  • Other laboratory tests are used to rule out diseases of the liver, pancreas and other abdominal organs as the cause of gastrointestinal symptoms.
  • A fecal examination is necessary to rule out parasitism, a common cause of diarrhea in cats and dogs. Sophisticated analysis of the feces for its protein and fat content may also be considered. Microscopic examination and culture of feces for certain bacteria may also be done.
  • Thoracic (chest) radiographs (x-rays) are needed to evaluate the size/shape of the esophagus, assess for the presence of a foreign object or growth, and assess the lungs for the possibility of secondary pneumonia, which may develop with esophageal disease.
  • Abdominal x-rays are very helpful in assessing the GI tract. They help to identify enlargement, dilation, and twisting of the stomach and intestines, the presence of fluid and gas within the GI, displacement of the GI tract, the presence of a foreign body or foreign material, and may provide clues to the presence of a tumor. Abdominal x-rays also help to rule out other abdominal diseases and other causes of the animal’s clinical signs.
  • Abdominal ultrasonography is also helpful in evaluating the GI tract. It is a noninvasive procedure that provides information about the GI tract and all the other abdominal organs. Your veterinarian may refer your dog to a veterinary internal medicine specialist for an abdominal ultrasound.
  • Certain x-ray procedures can be performed that are designed to assess the interior of the GI tract. These tests involve the swallowing or administration by tube, of a substance such as barium, that shows up white on x-rays. These x-ray tests are called positive contrast procedures. Examples of positive contrast procedures include an esophagram (barium swallow), an upper GI series, and a barium enema. These tests evaluate the lining of the GI tract and may detect the presence of a stricture (narrowing), dilation, obstruction, foreign body, mass or ulcers.
  • Positive contrast studies can also be performed under a type of video x-rays, called fluoroscopy. Fluoroscopy provides a way to watch the movement of the barium material as it passes through the pharynx, the esophagus and stomach. It provides information on the muscular coordination of these structures. Fluoroscopy is only available at certain referral practices and institutions, because it requires specialized, expensive equipment. Your veterinarian may refer your dog to a veterinary internal medicine specialist or a veterinary radiologist for performance of these tests.
  • Advanced imaging tests such as CT scan, radio-isotope scans, and MRI may be helpful in assessing the abdominal gastrointestinal tract and nearby organs.
  • Endoscopy and biopsy of the upper and/or lower bowel are often performed when GI tract diseases are suspected. Endoscopy involves the passage of a flexible viewing tube into the upper or lower portion of the GI tract. The interior of the esophagus, stomach, duodenum, anal canal, rectum and lower colon can be examined through endoscopy. Biopsies of the lining of these structures can be obtained through the endoscope, and submitted for microscopic evaluation. Sometimes foreign bodies of the esophagus and stomach can be removed via endoscopy. Biopsies can also be taken of masses that are growing into the center or lumen of these structures. General anesthesia is necessary for endoscopy; however, it is considered a relatively low risk procedure compared to abdominal surgery. This procedure may require the expertise of a specialist and specialized equipment.
  • Surgical exploration of the abdomen is sometimes needed to examine the GI tract, to establish a diagnosis, and to provide effective treatment of certain GI diseases. The entire abdominal GI tract can be examined by surgically opening the abdomen, and biopsies can be taken from both the inside or from the walls of the GI tract, as well as from surrounding structures.
  • Diseases of the GI tract are sometimes difficult to confirm, and may require a combination of many of the above tests in order to reach a diagnosis.

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