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Without ever leaving Baltimore, you can help save lives around the world. Today, diseases such as Travelers’ Diarrhea, Malaria, West Nile, Dengue Fever, Influenza and Respiratory Illnesses are hurting people all over the world. If you are 18-50 years old, you could help develop new vaccines. The Center for Immunization Research (CIR) offers both inpatient and outpatient vaccine studies. Visit our currently enrolling studies page for more intormation.You will be paid for your time.

To learn more about our research studies click one of the disease categories below:

Traveler’s Diarrhea

Enteric Diseases

Enteric diseases are diseases of the gastrointestinal tract (gut).  The CIR is interested in researching infectious diseases that affect the gut, primarily those that cause diarrheal illness. Enteric studies at the CIR are focused on ways to prevent or decrease the number of episodes of diarrhea through vaccine research and challenge models.  One of the CIR’s main areas of research is diarrheal illness caused by Enterotoxigenic E. coli (ETEC).

The main causes of diarrheal illness are pathogenic (disease-causing) bacteria, or germs, including Campylobacter, Enterotoxigenic Escherichia coli (ETEC), and Shigella. Diarrheal illness most commonly affects children and the elderly living in developing countries’ and travelers who visit developing countries (we call this travelers’ diarrhea). Travelers’ diarrhea primarily affects US military personnel and tourists. Diarrheal illness has been the largest cause of death and illness in children.  Diarrheal illnesses kill nearly 1.7 million children yearly and cause hospitalization of millions.  Repeated bouts of diarrhea and persistent illness, from 2 to 10 episodes of diarrhea per year per child, can greatly impair gut function.  This can also lead to long term developmental and health problems.  Diarrheal illness is also the single greatest cause of childhood malnutrition and growth retardation. 

Diarrheal illness can resolve on its own. Among healthy adults, acute illnesses usually end on their own within three to five days.  However, half of those adults infected report a decrease in job performance and one in ten will go on to develop post-infectious irritable bowel syndrome (IBS).  In the elderly population, diarrheal illness can cause serious illness and death.

History of E coli:

Diarrhea and dysentery cause major medical problems in military personnel, but it was not until after World War II that travelers’ diarrhea was clearly seen as a problem.  Studies in the 1950s and 1960s identified diarrhea as the most common cause of illness in travelers’ visiting less developed countries.  These studies did not connect the majority of illness with commonly known bacterial and viral pathogens.  Around the same time, it also became clear that a large number of diarrhea illnesses occurring in infants in developing countries were going undiagnosed.

As evidence began to increase it was discovered that diarrheal illness was caused by bacteria and research identified certain types of E. coli as the cause.  One such organism was known as Enteropathogenic E. coli.  Blood tests were used to identify E. coli as the cause of an outbreak of diarrhea in British soldiers in the mid 1960s.  It was then recognized that a specific type of E. coli was most often found in the stools of soldiers with diarrhea.  This type of E. coli was not previously identified in the “Enteropathogenic” group and was a key to a new origin of diarrhea.

Geographical Distribution:

People usually get travelers’ diarrhea on trips to Latin America, the Caribbean, Southeast Asia, Africa, Eastern or Southern Europe. As the map shows, the risk varies with your destination. Even travelers on cruise ships are at risk, as recent outbreaks have shown.

Enterotoxigenic E. coli (ETEC):              

E. coli are Gram-negative, rod-shaped bacterium propelled by long, rapidly rotating flagella (photo credit ).                                               

Most Escherichia coli (E. coli) bacteria are normally found in our environment and gut and do not cause disease.  This is because it is a part of the normal flora of the mouth and gut. This helps protect the gastrointestinal (GI) tract from bacterial infections, aids in digestion, and produces small amounts of vitamins B12 and K.  The germ, which is also found in soil and water, is widely used in many different types of laboratory research. It is also the most common member of the Escherichia family, named for Theodor Escherich, a German physician. 

There are many different types of E. coli germs causing diarrheal illness These germs have the ability to take over the GI tract and cause diarrhea in humans and animals.  The most common is Enterotoxigenic E. coli (ETEC).  ETEC causes illness by attaching itself to the intestinal lining through specialized projections called fimbriae.  Once attached, ETEC multiply and make toxins that cause an increase of intestinal fluids, which can cause diarrhea and dehydration.  ETEC is the most common cause of travelers’ diarrhea and causes many foodborne outbreaks in the U.S. each year.   ETEC is spread by poor hygiene (lack of good hand washing), and through food or water polluted with human or animal feces.  Less commonly, ETEC can also be spread from person to person.

About ETEC:

In developing countries, ETEC is the leading cause of infectious diarrhea.  A person may become infected with ETEC through ingestion of contaminated food and water.  Each year, ETEC causes sudden diarrheal illness in several hundred million people and results in more than 600,000 deaths.  ETEC is also the most common cause of travelers’ diarrhea in people traveling from industrialized countries to less developed countries.  The incidence rates for those traveling are as high as 0.5 episodes per person over 1-2 weeks of initial contact.

Symptoms:

The severity of ETEC diarrhea can range from mild discomfort to severe dehydration and illness.  Symptoms may also include watery diarrhea, vomiting, nausea, headaches, abdominal pain and/or cramps, gas, bloating, lightheadedness, muscle/body aches, physical discomfort, chills, tiredness, loss of appetite, fever, and severe fluid loss.

Why create an ETEC vaccine: 

Currently, quick replacement of fluids is the ideal therapy for those who have significant fluid and electrolyte loss.  ETEC can also be treated with antibiotics, which have been successful in greatly shortening the illness.  However, ETEC is increasingly becoming more and more resistant to antibiotics, which is another cause of great concern.  The development of a vaccine to prevent this disease could decrease the rate of resistance and help those still in need of antibiotic treatment.

Currently, there is no licensed vaccine that provides a safe, effective mode of prevention.   Development of an effective preventative agent to control ETEC diarrhea could be a useful product, especially to those living in less developed countries, travelers and military personnel going into high-risk areas such as Latin America, Africa, and Asia.  The development of an ETEC vaccine could also significantly lower illness and morbidity rates and save the lives of children and the elderly in developing countries.

Progress towards an ETEC vaccine:

The principal investigator and the Enteric team work with a number of academic, industry, military, and government partners to achieve the goal of developing new vaccines against bacterial diarrhea.

At this time, we are focused on developing a vaccine that would block attachment and toxin activity.  This would hopefully interrupt the infection at its earliest stages, which should reduce the number and severity of ETEC diarrhea cases.

To learn more about participating in a vaccine clinical trial, visit our ENROLL now page or you may contact us at (410-955-7283) (toll free 877-863-1374).

Resource Links:

http://www.encylopedia.com/

http://www.citahealth.com/medical/travel/diseases/dukoral.html

http://www.who.int/foodsafety/foodborne_disease/ecoli.pdf

http://www.who.int/vaccine_research/diseases/e_e_coli/en/

http://www.gatesfoundation.org/topics/Pages/diarrhea.aspx

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Shigella/Shigellosis:

Shigellosis is an infectious disease caused by a group of bacteria called Shigella.  The Shigella bacteria can infect the digestive tract and cause a wide range of symptoms.  When infected with Shigella most people develop diarrhea (often bloody), fever, and stomach cramps. Symptoms usually start a day or two after coming in contact with the bacteria.  Infections called Shigellosis sometimes goes away on its own, usually within 5 to 7 days. 

Shigellosis is endemic throughout the world.  Worldwide there are about 164.7 million cases of which, 163.2 million cases are in developing countries and 1.5 million are in industrialized countries.  Each year, 1.1 million people are estimated to die from Shigellosis and 580,000 cases of Shigellosis are reported among travelers and military personnel.  A total of 69% of all episodes and 61% of all deaths related to Shigellosis involve children less than 5 years old.  Shigellosis is also responsible for some 120 million cases of severe dysentery, A majority of these cases occurring in developing countries and involve children less than 5 years old. 

Each year, there are about 14,000 laboratory-confirmed cases of Shigellosis.  About 450,000 total cases (85% due to S. sonnei) in the United States.  Since many of the milder cases are not diagnosed or reported, the actual number of illnesses may be twenty times greater.  Persons with Shigellosis in the United States rarely need hospitalization and some people who are infected may have no symptoms, but they can still pass the bacteria to others.  In some people, mostly young children and the elderly, the diarrhea can be so severe that the person needs to be hospitalized.   Shigellosis is common and causes recurrent problems in settings where hygiene is poor and can sweep through entire communities.  In the developing world, Shigellosis is more common and is present in most communities.  Shigella is also more common during the summer months then in the winter. 

Children, especially toddlers aged 2-4, are most likely to get Shigellosis.  Many cases are related to the spread of illness in child-care settings, and among families with small children.  Severe illness, with a high fever may result in seizures in children less than 2 years old.  Infants younger than 6 months old rarely develop Shigellosis.

Illnesses from Shigella are spread very easily and can be prevented with good hand washing.

(Source: http://en.wikipedia.org/wiki/Shigella )

Shigella is a genus of gamma proteobacteria in the family.Enterobacteriaceae.  Shigellae are gram-negative, nonmotile, non-spore forming, rod-shaped bacteria, which are very closely related to Escherichia coli.

 What sort of germ is Shigella:

Classifications

Serogroup AS. dysenteriae (12 serotypes)

Serogroup BS. flexneri (6 serotypes)

Serogroup CS. boydii (23 serotypes)

Serogroup DS. sonnei (1 serotype)

The germ (Shigella) is a family of bacteria that can cause diarrhea and it is naturally found in humans and apes.   Shigella are microscopic living creatures that pass from person to person.  Shigella was discovered in 1898 by a Japanese microbiologist named Kiyoshi Shiga, for whom the genus is named. 

There are four different types of Shigella bacteria:  S. dysenteriae, S. flexneri,   S. boydii, and S. sonnei.  Shigella sonnei, also known as “Group D” Shigella, accounts for over two-thirds of Shigellosis in the United States. It’s also the main cause of most Shigellosis in industrialized countries where it accounts for 77% of cases.  Shigella flexneri, or “Group B” Shigella, is widespread in about 60% of developing countries and are the most frequently isolated species worldwide.  Other types of Shigella are rare in this country, though they continue to be important causes of illness in the developing world.  One type found in the developing world, Shigella dysenteriae type 1, can cause deadly epidemics in developing regions.   Outbreaks of dysentery due to S. dysenteriae type 1 are frequent in poorer population’s living in crowded or confined settings where hygiene is poor and sanitation is nearly non-existent, such as refugee camps.  Acute complications may occur, which include peritonitis and septicemia, especially in malnourished children, and severe Hemolytic Uremic Syndrome (HUS) with renal failure.  Since the late 1960’s, pandemic waves of Shigella dysentery have hit sub-Saharan Africa, Central America and South and South-East Asia, often striking areas of political upheaval and natural disaster.  During the 1994 genocide in Rwanda, approximately 200,000 refugees who fled into the North Kivu region of Zaire, died in one month from dysentery caused by a strain of S. dysenteriae. This strain was resistant to all commonly used antibiotics. 

How people get Shigella/Shigellosis:

Shigellosis is very contagious and is spread from human to human by the fecal oral route.  Most Shigella illnesses are the result of the bacteria passing from stools or soiled fingers of one person to the mouth of another person (fecal oral route).  This happens when basic hygiene and hand washing habits are poor, or through certain types of sexual activity.   Shigellosis can also be spread though contaminated food and water.  This is often seen in travelers and military troops, deployed in camps with poor hygiene conditions.  A person may also become infected by coming into contact with something contaminated by the stool from another infected person.  Illness is easily spread to family members and playmates of children who are at high risk of becoming infected.  The bacteria may also spread in water supplies in areas where there is poor sanitation.  Shigella can even be carried and spread by flies that have touched contaminated stools.

Shigellosis can also be caused by eating contaminated food.  Contaminated food usually looks and smells normal.  Food may become contaminated by infected food handlers who did not wash their hands with soap after using the bathroom.  Vegetables can become contaminated if they are harvested from a field with sewage in it.  Flies can breed in infected feces and then contaminate food.  Water may become contaminated with Shigella bacteria if sewage runs into it or if someone with Shigellosis swims or plays in the water. Illness can then be caused by drinking, swimming in or playing with the contaminated water.

It does not take many Shigella germs to cause an illness.  Shigella are present in the stools of an infected person while they are sick.  In addition, Shigella can be passed in a person’s stool for about 4 weeks, even after the symptoms of illness have ended.

Signs and Symptoms:

The bacteria (Shigella) produce toxins that can attack the lining of the large intestines, causing swelling, ulcers on the intestinal wall, and bloody diarrhea.  The severity of diarrhea sets Shigellosis apart from regular diarrhea.  In both children and adults with Shigellosis the first bowel movement is often large and watery.  Later bowel movements may be smaller, but the diarrhea may have blood, mucus, or pus in it.  Illness is usually characterized by a short period of watery diarrhea with intestinal cramps and general aches, soon followed by bloody stools.  Other symptoms include but are not limited to abdominal cramps, fever, headache, loss of appetite, fatigue, gas, nausea, vomiting, and painful bowel movements.  In very severe cases, a person may have convulsions (seizures), a stiff neck, severe headaches, extreme tiredness and confusion. Shigellosis can also lead to dehydration and in rare cases, other complications, like arthritis, skin rashes, and kidney failure.  Symptoms can take as long as a week to show up, but usually begin two to four days after ingestion of the bacteria.  Symptoms usually last for several days, but can last for weeks.

Diagnosis:

Many different kinds of germs can cause diarrhea, so finding the cause will help aid in proper treatment.  Determining if Shigella is the cause of the illness depends on laboratory tests that identify Shigella in the stools of an infected person. The laboratory can also do specialized tests to determine which specific type of Shigella is involved and which antibiotics, if any, would be best for treatment.

Treatment:

Shigellosis can be treated with antibiotics and fluids if felt necessary.  People with mild illnesses usually recover quickly without antibiotic treatment.  However, if a person is treated with the right type of treatment, this may kill the Shigella bacteria, and may shorten the illness by a few days.  The antibiotics commonly used are ampicillin, trimethoprim/sulfamethoxazole (also known as Bactrim or Septra), or among adults ciprofloxacin.  Some Shigella bacteria have become resistant to antibiotics.  This means some antibiotics might not be a helpful form of treatment for some individuals.  Inappropriately using antibiotics to treat Shigellosis can sometimes make the germ more resistant.  Therefore, when several people in the community are affected by Shigellosis, antibiotics are sometimes used selectively to treat only the more severe cases.  Anti-diarrheal medications such as loperamide (Imodium) or diphenoxylate with atropine (Lomotil) can make the illness worse and should be avoided.

Long term consequences:

A person with diarrhea caused by Shigella, usually recover completely, although it may be several months before their bowel habits are entirely normal.  About 3% of people infected with one specific type of Shigella called, Shigella flexneri, can later develop pains in their joints, irritation of the eyes and painful urination.  This is called post-infectious reactive arthritis or Reiter’s syndrome.  It can last for months or years, and can lead to chronic arthritis.  Post-infectious arthritis is caused by a reaction to the Shigella illness that happens only in people who are genetically prone to it.  Once a person has had Shigellosis, they are not likely to get infected with that specific type again for at least several years.  However, they can still get infected with other types of Shigella.

Prevention:

Currently, there is no vaccine to prevent Shigellosis.  The spread of Shigella from person to person can be reduced by frequent and careful hand washing, which is important among all age groups.  Hand washing among children should be done on a regular basis and supervised by an adult, especially among children who have not yet been fully toilet trained.  Basic food safety and disinfection of drinking water helps prevent Shigellosis caused by polluted food and water.  Proper handling, storage, and preparation of food can aid in prevention of the illness.  Cold foods should be kept cold and hot foods should be kept hot to prevent bacterial growth.  People with Shigellosis should not prepare food or drinks for others, until they have been shown to no longer be carrying the bacteria, or if they have had no diarrheal stools for at least 2 days. 

When traveling to an undeveloped country, other simple precautions can be taken to help prevent Shigellosis also.  Those precautions include only drinking treated or boiled water, and eating only cooked hot foods or fruits you washed and peeled yourself or were canned.  The same precautions prevent other types of travelers’ diarrhea also.  In the United States and other developed countries the treatment of water supplies (drinking water) and sewage systems have been in place for many years, and have been successful in prevention.  In less developed countries they don’t have this type of water treatment prevention, which in turn has made the risk of illness greater for those living and traveling in those areas.

Why Develop a Shigella Vaccine:

In the absence of an effective vaccine, the increasing rate of antibiotic resistant Shigella strains worldwide has become a major cause of concern.  A survey of 600,000 people residing in Bangladesh, China, Pakistan, Indonesia, Vietnam, and Thailand, showed that Shigella was present in 5% of the 60,000 diarrhea episodes detected and the majority of the bacterial isolates were resistant to amoxicillin and cotrimoxazole.  Similarly, during a 36-month surveillance study in a rural district in Thailand, 95% of the S. sonnei and S. flexneri isolates were resistant to tetracycline and cotrimoxazole.  In addition, 90% of the S. flexneri isolates were also resistant to ampicillin and chloramphenicol.  A similar finding was also made in North Jakarta, Indonesia, where a surveillance study found that children 1 to 2 years old who had high occurrence rates of Shigellosis had a 73% to 95% resistant rate to ampicillin, trimethoprim/sulfamethoxazole, chloramphenicol and tetracycline.

Shigellosis, which continues to have an important global impact, can not be adequately controlled with the current prevention and treatment measures.  Innovative strategies, including the development of vaccines against Shigella, could provide substantial benefits, to public health programs, military personnel, travelers, and those living in undeveloped countries.  Development of a successful Shigella vaccine could significantly lower morbidity rates and save lives.

To learn more about participating in a vaccine clinical trial, visit our ENROLL now page or you may contact us at (410-955-7283) (toll free 877-863-1374).

Resouce Links:

http://www.cdc.gov/nczved/divisions/dfbmd/diseases/shigellosis.html 

http://textbookofbacteriology.net/themicrobialworld/Shigella.html

The US Center for Disease Control and Prevention:  http://www.cdc.gov/malaria/index.html

The World Health Organization: http://www.who.int/malaria/en/

The Malaria Vaccine Institute: http://www.malariavaccine.org/

The Johns Hopkins Malaria Research Institute: http://malaria.jhsph.edu/research/

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West Nile:

Please check back later to learn more about West Nile vaccine clinical trials.

To learn more about participating in a vaccine clinical trial, visit our ENROLL now page or you may contact us at (410-955-7283) (toll free 877-863-1374).

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 Dengue:

About Dengue Disease:

Dengue (pronounced DENG-gay) is a disease caused by infection with the dengue virus.  Dengue infection can cause two forms of the disease: Dengue Fever or Dengue Hemorrhagic Fever/ Shock Syndrome (DHF/DSS).

Dengue fever is also known as ‘breakbone fever’ because it can cause extreme pain in the joints and muscles.Dengue Hemorrhagic Fever/ Shock Syndrome (DHF/DSS) occurs less commonly than dengue fever but is a more serious form of dengue infection that can result in death. The symptoms of dengue fever and DHF/DSS are described below.

According to the World Health Organization (WHO), dengue viruses cause more than 50 million cases of dengue fever and about 500,000 cases of DHF/DSS every year.  Infection with dengue viruses is the leading cause of hospitalization and death in children in at least 8 tropical Asian countries.

There are no specific medicines to treat or prevent dengue. Health care providers treat dengue by managing the symptoms of illness such as dehydration and fever.

Dengue Virus:

Dengue virus is spread to people by mosquitoes such as Aedes egypti and Aedes albopticus. The virus is transmitted to mosquitoes when they bite someone who is infected with dengue. The mosquito then has to bite a person to spread the disease.   

Dengue virus is related to other mosquito-borne viruses such as Yellow Fever, West Nile, St. Louis Encephalitis and Japanese Encephalitis (family Flaviridae, genus Flavivirus).

There are 4 forms (serotypes) of dengue virus (DEN1, DEN2, DEN3, and DEN4).

Geographical Distribution

Dengue is typically found in tropical and sub-tropical parts of the world such as:

  • South and Central America
  • Southeast Asia
  • Sub-Saharan Africa
  • Indonesia

In these parts of the world, dengue is mostly found in urban and semi-urban areas.The map below shows parts of the world where dengue was likely to be transmitted in 2008. These areas continue to be at risk for dengue transmission.

There have been some cases of dengue illness reported in Europe. In most of these cases, people are infected during travel to areas of the world where dengue is found. There have also been a few reports of people who have become ill with dengue without having traveled to places where the disease is found. For example, in September 2010 there were two cases of local dengue infection within France Scientists think that these people were bit by mosquitoes that were infected with the dengue virus in France.

Dengue in the US:

Most cases of dengue in the US occur in people returning from travel in other parts of the world where dengue is found. A few cases of local infection have been reported. Most of these cases occurred along the Texas-Mexico border and are thought to have been introduced from Mexico.

Since September 2009, there have been some cases of local dengue infection reported in Key West, Florida. This raises concerns that dengue could become more widespread in the continental US, especially because Aedes mosquitoes, which spread dengue, are found in the southern and southeastern US.

Symptoms:

Most dengue infections cause no symptoms, but sometimes dengue can cause mild to life-threatening illness.  For example, illness with one type of dengue infection followed by an illness with a different type of dengue infection can cause serious life threatening illness, DHF/DSS.  Any suspected dengue infection should be reported as soon as possible to a health care provider.  

Dengue Fever Symptoms:

A classic symptom of dengue fever is a sudden high fever, lasting about 5 days. In general, fever is defined as a body temperature higher than 100° Fahrenheit..

According to the Centers for Disease Control and Prevention (CDC), a diagnosis of dengue fever is made when someone who has recently been in a high risk area has a high fever accompanied by at least two of the symptoms listed below:

  • Severe headache
  • Severe eye pain (behind eyes)
  • Joint pain
  • Muscle and/or bone (joint) pain
  • Rash
  • Mild bleeding or easy bruising
  • Low white cell count

Dengue Hemorrhagic Fever/Shock Syndrome (DHF/DSS) Symptoms:

DHF/DSS occurs much less commonly than dengue fever. In the early stages of infection, the symptoms of DHF/DSS are similar to those of dengue fever. However, as the fever declines severe bleeding under the skin and inside the body will occur. As a result of the bleeding, failure of the circulatory system may occur and the infected individual may go into shock and possibly die.

According to the CDC, Symptoms of DHF/DSS may include:

  • Severe abdominal pain or persistent vomiting
  • Red spots or patches on the skin (called petechiae)
  • Bleeding from the nose or gums
  • Vomiting blood
  • Black, tarry stools (feces, excrement)
  • Drowsiness or irritability
  • Pale, cold or clammy skin
  • Difficulty breathing

Why develop a dengue vaccine?:

Approximately 2 billion people in the world are at risk of dengue virus infection. There is no licensed vaccine to protect people from dengue infection. Currently, the best way to prevent dengue infection is by controlling mosquitoes and preventing mosquito bites. Mosquito control is expensive and is sometimes not effective. A dengue vaccine would be an affordable and effective way to prevent dengue infections and save lives. The WHO has made the development of a dengue vaccine a top priority (Resolution ).  

Progress towards a vaccine:

An effective dengue vaccine will need to provide long-term protection against each of the four dengue serotypes (DEN1, DEN2, DEN3 and DEN4) in order to decrease the risk of DHF/DSS.

At the CIR, we have been studying experimental dengue vaccines in human volunteers since 1999. The vaccines are developed with scientists at the National Institutes of Health (NIH). These live-attenuated virus vaccines contain a weakened form of the dengue virus.  

Vaccines for each of the four forms of dengue (DEN1, DEN2, DEN3 and DEN4), have been studied separately. These are called monovalent vaccines.  In 2010 we started early-stage studies for a vaccine that contains vaccine virus for all four dengue serotypes. This is called a tetravalent vaccine.

Other companies in the US and abroad are also doing studies to make a dengue vaccine. Most dengue vaccine studies are in the early phase of clinical research studies.   

Participating in a Dengue Vaccine Study at the CIR:

Common Study Designs

We have different study designs, including:

  • Single-dose vaccine studies: Volunteers will get one shot of vaccine (or placebo) and attend follow-up visits. These studies usually last about 6 weeks to 6 months
  • Multiple-dose vaccine studies: Volunteers will get two or more doses of vaccines (or placebo) and attend follow-up visits. The shots are usually given 4 to 6 months apart and the studies last about 5½ to 7½ months
  • Monovalent vaccine studies: Volunteers will get vaccine that has vaccine virus for only one type of dengue
  • Tetravalent vaccine studies: Volunteers will get vaccine that has vaccine virus for all 4 types of dengue
  • Before agreeing to join a study, volunteers will be given an informed consent form which gives specific information about the study.

Follow-Up:

After getting the study shot (vaccine or placebo) volunteers will be asked to come back to the clinic for visits to evaluate their health. An example of a typical schedule is shown below.

At the follow-up visits we may do one or more of the following:

  • Draw blood to do tests to assess health
  • Collect vital signs such as temperature, blood pressure, pulse and breathing rate
  • Conduct a physical exam
  • Conduct a pregnancy test for females

Volunteers may also be asked to keep a memory card (like a diary) to record temperatures and/or any symptoms.

Sample Visit Schedule:

Optional Skin Biopsy:

One of the possible side effects of the dengue vaccine is a temporary rash.  To learn more about how the dengue vaccine affects the skin, we might ask some volunteers to take part in an optional skin biopsy sub-study. A skin biopsy is a procedure in which a small skin sample is collected and studied.

The biopsy is done using a sharp punch as shown in the picture. The size of the biopsy is about the size of a pencil eraser. First, a numbing medicine is applied to the skin where the biopsy will be performed. No stitches are needed after the procedure. The biopsy site is covered with a band-aid and should remain covered for 5-7 days until the skin has healed. The biopsy usually heals over 2-3 weeks.

Skin Biopsy:

Before agreeing to the skin biopsy, volunteers will be given an informed consent form which explains the skin biopsy sub-study.

We welcome your interest in dengue vaccine studies at the CIR. To participate in a dengue vaccine study, you need to be a healthy adult between the ages of 18-50 years.

To learn more about participating in a vaccine clinical trial, visit our ENROLL now page or you may contact us at (410-955-7283) (toll free 877-863-1374).

La Ruche G, Souarès Y, Armengaud A, Peloux-Petiot F, Delaunay P, Desprès P, Lenglet A, Jourdain F, Leparc-Goffart I, Charlet F, Ollier L, Mantey K, Mollet T, Fournier JP, Torrents R, Leitmeyer K, Hilairet P, Zeller H, Van Bortel W, Dejour-Salamanca D, Grandadam M, Gastellu-Etchegorry M. First two autochthonous dengue virus infections in metropolitan France, September 2010. Euro Surveill. 2010;15(39):pii=19676. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19676

 Paramyxoviruses are a family of viruses that cause diseases such as measles, mumps, and respiratory illnesses that range from the common cold to pneumonia (infection in the lungs).  At the Center for Immunization Research, we focus on paramyxoviruses that cause respiratory illness; namely, Respiratory Syncytial Virus (RSV), Human Metapneumovirus (HMPV), and Parainfluenza viruses (HPIV).  These viruses can cause serious illnesses such as croup, wheezing, bronchiolitis (swelling of the lower lungs), and pneumonia resulting in many hospitalizations every year in young children and the elderly.  Even though measles and mumps are prevented through vaccine administration (MMR), licensed vaccines for RSV, HMPV, or HPIV are not available at this time.  With a licensed vaccine, the severity of these illnesses could possibly be reduced through individual immunity and a decrease in the spread of the viruses.

About the diseases

Parainfluenza viruses (HPIV):       

There are 4 identified strains or types of HPIV (HPIV1, HPIV2, HPIV3, HPIV4).  At the CIR, we study vaccines for strains 1-3.  Even though they are all very similar in the complications they produce, there are some differences between strains.  These differences are: the time of the year they occur, the age group that is most at risk, and how much illness they produce compared to other respiratory illness viruses.  HPIV1 is a leading cause of viral croup, pneumonia, and bronchiolitis in children under 6 years of age.  About 6% of all pediatric hospitalizations are for respiratory tract diseases caused by HPIV1.  Infections mostly occur in the autumn months, every other year in the odd years (for example, 2009, 2011, 2013, etc.).  Children under 6 years of age and people with very weakened immune systems seem to be at higher risk for complications from HPIV1 infections. 

HPIV2 occurs mostly after 6 months of age.  It often happens in even years (for example, 2010, 2012, 2014, etc.) in the autumn months.  HPIV2 also causes upper respiratory and lower respiratory illness. 

HPIV3 usually infects infants in the first 4 months of life and occurs year-round, mostly in the spring months.  It is the 2nd leading cause of hospitalization of infants and young children for viral respiratory tract disease worldwide.

Human Metapneumovirus (HMPV):  HMPV was discovered in 2001, although it has been in humans for at least 50 years, and can be found worldwide.  In healthy adults, infection with HMPV may cause upper respiratory illness with symptoms such as headache, cough, and/or fatigue.  Symptoms in infants and young children are the same as with RSV (see below),  and can include more severe complications such as, otitis media (ear infections), bronchiolitis, croup, pneumonia, and episodes of wheezing in children with asthma.  Children less than 2 years of age are most likely to have severe HMPV infections.  HMPV causes 5 to 10% of pediatric hospitalizations for viral pneumonia and bronchiolitis, and up to 12% of children with lower respiratory illness to visit a doctor’s office. 

Respiratory Syncytial Virus (RSV):  In healthy children and adults, RSV infection can cause cold-like symptoms or no symptoms at all.  But in infants (especially premature ones) or children with weakened immune systems, it can cause more severe upper respiratory symptoms, such as bronchitis or croup, and lower respiratory infections like bronchiolitis and pneumonia.  It is the main cause of hospitalizations from respiratory illness.  RSV infects infants mostly in the first 4 months of life and mostly happens in the fall, winter, and early spring of every year.  Between 25% and 40% of infants with upper respiratory infection will get worse and develop lower respiratory infections.

For more information on RSV, visit the CDC website:  http://www.cdc.gov/rsv/clinical/description.html

Geographical Distribution: 

Paramyxoviruses cause illness around the world.  The Center for Disease Control (CDC) keeps track of these illnesses in the U.S.  An example of some RSV infections in Maryland (from November 2009-October 2010) is shown below.  Notice that the highest cases of RSV occurred from November 2009 to March 2010 then decreased to very few (or almost none) for the rest of the year. 

                   

 Why create a vaccine? 

There is no specific treatment for these viral infections.  The symptoms (such as fever, cough, runny nose) and complications (such as pneumonia) can only be treated as they occur.  For premature infants and children with a weak immune system, there is a preventative treatment available for RSV called Palivizumab (pah-lih-VIH-zu-mahb).  Palivizumab is a treatment that uses laboratory made antibodies to trigger the immune system to help fight off RSV after exposure.  It may not prevent infection, but it helps to reduce the severity of the disease.  It is a shot given monthly during the RSV season to at risk infants and children.  There is no preventative vaccine or treatment for HPIV or HMPV.  Vaccines are important for the prevention of these diseases.

Progress towards a vaccine:

Since 1995, the CIR hase been working with the NIH to develop paramyxovirus vaccines and challenge viruses .  These investigational products, live virus vaccines or challenge viruses are weakened and given by nose drops to study volunteers.  Before the vaccines are studied in children, they are always tested in adults for safety reasons. 

Common designs for paramyxovirus studies: At the CIR, we may have many studies at different stages of development.

Challenge Studies: Before the paramyxovirus vaccines are tested, challenge viruses are given to adults in an unblinded study.  Unblinded means that investigators and volunteers know they are receiving the study virus.  Challenge studies are usually done in an inpatient unit because it may be possible for volunteers to pass the challenge virus to other people. 

Vaccine Studies: The paramyxovirus vaccine studies at the CIR are designed to be double-blind and placebo controlled.  This means that one group of volunteers receives the vaccine and another group receives placebo (salt water).  Neither the investigator nor the volunteer know whether they got the vaccine or placebo, so they are ‘blinded’.  This is the preferred design in research to test study vaccines.     

Study structure:  The first visit is called a screening visit.  After signing the screening consent form, we will get a medical history, complete some paperwork, and do a nasal wash and/or draw blood to find out if the volunteer has ever come in contact with paramyxoviruses before.  The nasal wash is a simple procedure where we put salt water into the nostrils, then let it drain out into a cup.  When drawing blood from children, we offer a numbing medication to  help make the procedure less painful.  Adult study visits take place at Hampton House or the CIR Bayview inpatient unit.  Pediatric study visits may be in the home, at the pediatrician's office, or at a CIR office.

Each study has specific requirements that must be met before a volunteer is accepted.  These requirements and the screening visit helps decide who can be in a study.  Some common reasons why someone  may not be able to participate in these studies include:

  • a previous history of recurrent wheezing or asthma
  • the volunteer lives with (or attends daycare with) a pregnant caregiver, a person with a weakened immune system, or as infant less than 6 or 12 months of age
  • developmental concerns
  • the volunteer is unable to attend every study visit 

After the screening visit and before receiving the study product, a separate study consent will need to be signed by the volunteer or parent.  Getting study vaccine or challenge virus always occurs in a medical facility.  This will most likely happen at the pediatrician’s office, Hampton House, or CIR Bayview inpatient unit. 

Follow up visits usually include a brief physical exam, vital signs, medical history, and a nasal wash.  Adults are seen for follow up visits at the Hampton House.  The children may be seen in the home.  Home visits usually last 15-20 minutes and are made by pediatric nurse practitioners or registered nurses.  Diary cards are often used to record daily temperatures and any medications. 

To learn more about participating in a vaccine clinical trial, visit our ENROLL now page or you may contact us at (410-955-7283) (toll free 877-863-1374).

Parents of children between the ages of 6 months and 5 years can contact us at 410-502-3333. 

Resource Links:

http://kidshealth.org/parent/infections/stomach/shigella.html

http://www.who.int/vaccine_research/diseases/diarrhoeal/en/index6.html

http://www.who.int/vaccine_research/diseases/shigella.html

http://www.britannica.com/

http://en.wikipedia.org/wiki/Shigella.html

http://emedicine.medscape.com/

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Malaria:

http://www.cdc.gov/malaria/malaria_worldwide/impact.html

One half of the world"s population (3.3 billion) live in areas at risk of malaria infection. In 2008 WHO estimated that up to 300 million people got sick with malaria. Each year, up to 1 million people, mostly children, die from malaria. Malaria is a parasitic infection spread by mosquitoes. There is no vaccine for malaria, but it can be prevented and treated. When a person is infected,early recognition and treatment can greatly lower the risk of severe disease.

Malaria is the 5th leading cause of infectious disease deaths worldwide. Malaria occurs in 109 countries and territories. Most infections happen in Africa where 89% of all malaria deaths occur.

About the disease:

The name for malaria comes from medieval Italian "mala aria" or "bad air." The disease was also called ague or marsh fever because it was found in swampy areas and marshlands. Malaria was once a significant problem in North America and Europe. In the 1940s and 1950s the US worked to reduce mosquito breeding areas. Through successful mosquito control, malaria was wiped out in those regions.We still have some Anopheles mosquitoes in the US, but they no longer cause malaria. Read more from the CDC about the history of malaria in the world.

Malaria is caused by infection with Plasmodium parasites. This parasite is carried by a certain type of mosquito called Anopheles. Humans are infected with the parasite when they are bitten by an infected mosquito. When this parasite multiplies in the blood a person can become ill will malaria. There are several species of Plasmodium parasites that can infect people. Plasmodium falciparum causes the most severe disease and death. Plasmodium ovale and Plasmodium vivax can hide in the liver and cause disease years after infection.

Symptoms:

Malaria disease can be categorized as uncomplicated, lasting about 6-10 hours with symptom consisting of hot, cold and sweating stages. Or, the disease can be more severe (complicated) with serious organ failures or abnormalities in the patient's blood or metabolism.

The symptoms of malaria can be rather non-specific. So, the diagnosis can be missed if health providers are not alert to the possibility of this disease. The most frequent symptoms of malaria include

  • fever and chills
  • headache
  • muscle aches
  • joint aches
  • weakness
  • vomiting and diarrhea.

Other clinical features may include:

  • enlarged spleen
  • anemia, low platelets
  • low blood sugar
  • problems with breathing
  • problems with kidney function
  • neurologic changes

Severe malaria occurs when infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism. The symptoms can vary a lot depending on the infecting species, the amount of parasites infecting and the immune status of the patient. Infections caused by Plasmodium falciparum can progress to severe, potentially fatal forms with:

  • central nervous system involvement (cerebral malaria)
  • acute kidney failure
  • severe anemia
  • adult respiratory distress syndrome.

The life cycle of Plasmodium is shown below:

Plasmodium life cycle  http://post.queensu.ca/~forsdyke/pfalcip01.htm

Treatment:

Treatment for malaria should not be initiated until the diagnosis has been confirmed by laboratory investigations. "Presumptive treatment" without the benefit of laboratory confirmation should be reserved for extreme circumstances (strong clinical suspicion, severe disease, impossibility of obtaining prompt laboratory confirmation).

Once the diagnosis of malaria has been confirmed, appropriate antimalarial treatment must be initiated immediately. Treatment should be guided by three main factors:

  • The infecting Plasmodium species
  • The clinical status of the patient
  • The drug susceptibility of the infecting parasites as determined by the geographic area where the infection was acquired

Additional information for the treatment of malaria in the United States can be found at the CDC website.

 Geographical Distribution:

Cases of malaria in the U.S. usually occur in people who have traveled to other parts of the world where malaria is wide spread. 

Why create a malaria vaccine?:

A malaria vaccine would greatly help childhood health by reducing severe disease and death throughout much of Africa and other parts of the developing world. Currently, there is no licensed vaccine for malaria. 

Progress towards a vaccine:

There are several barriers to malaria vaccine development.  Mostly, technical and financial difficulties have prevented a vaccine from being developed. The complex life cycle of the parasite and the human immune response to malaria infections make it very hard to develop a vaccine.  In recent years creating a malaria vaccine has been prioritized by the global community. As a result, more money is now is invested in vaccine research.

Several vaccines are currently being studied. The most clinically advanced malaria vaccine is currently in  in Africa. This vaccine has been shown in earlier studies to be safe and to reduce severe malaria in children 5-17 months old by 50%.  Read more about malaria vaccines being created at Sanaria, the National Institutes of Health, and GlaxoSmithKline.Researchers  hope to have a malaria vaccine available by 2025 that will be more than 80% effective against disease.

Common Malaria study designs at the Center for Immunization Research (CIR):

Several malaria vaccines have been studied at the CIR. Mot recently, BSAM, a malaria vaccine made of two surface proteins was tested in a Phase I study in the CIR Washington, DC location and in Mali. The BSAM vaccine was given to volunteers in three increasing doses (at 0.2 and 6 months). Volunteers are currently in long-term follow-up.

Participation in a malaria vaccine study:

Screening:  Before vaccination, a volunteer’s health is assessed by medical history, physical exam, and lab tests (blood and urine).

Vaccination and Follow-up:  If eligible, volunteers will get the vaccine or placebo. After vaccination volunteers are followed closely to look for any side effects. Volunteers come back at certain times for blood work (lab tests) to assess health and measure the immune response to the vaccine. 

The duration of the specific study may vary. typically, a malaria study may last between 6 months to 2 years. volunteers will be told how long the study will last.

For more information about our current malaria studies vist the CIR Studies page.

To join a CIR Vaccine research Study click HERE.

Johns Hopkins School of Public Health (JHSPH) CIR Malaria Publications:

  • Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults. PLoS One. 2010 Jan 22;5(1):e8787.
  • A Phase] 1 study of the blood-stage malaria vaccine candidate AMA1-C1/Alhydrogel with CPG 7909, using two different formulations and dosing intervals.  Vaccine. 2009 Jun 24;27(31):4104-9. Epub 2009 May 15.
  • Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLoS One. 2008 Jul 9;3(7):e2636.

To learn more about participating in a vaccine clinical trial, visit our ENROLL now page or you may contact us at (410-955-7283) (toll free 877-863-1374).

Parents of children between the ages of 6 months and 5 years can contact us at 410-502-3333. 

Resource Links:

http://www.who.int/vaccine_research/diseases/e_e_coli/en/

http://www.gatesfoundation.org/topics/Pages/diarrhea.aspx

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Influenza

Please check back later to learn more about Influenza vaccine clinical trials.

To learn more about participating in a vaccine clinical trial, visit our ENROLL now page or you may contact us at (410-955-7283) (toll free 877-863-1374).

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