HOW SLEEP BENEFITS BRAINS
Ah-h-h. There is nothing like a good night's sleep. You feel refreshed and ready for the day. But did you know that during sleep you are enhancing your learning and memory? Did you know that you would probably do better on an exam if you had a good night's sleep versus pulling an all-nighter? Find out more about the surprising benefits of sleep and how you can make the most out of those blissful hours.
Sleep Enhances Brain Connections in Early Development-Study
Animal studies show that sleep dramatically enhances changes in brain connections during a period of early development. Researchers at the University of California, San Francisco, examined the effect of sleep on brain plasticity in young cats that had just experienced an environmental challenge. The animals that were allowed to sleep for six hours after the stimulation developed twice the amount of brain change, compared to cats kept awake afterward. "This is the first direct evidence that sleep modifies the effect of environmental stimuli on the development of new brain connections," said Marcos G. Frank, Ph.D. The finding has broader implications for plasticity in the brains of adult animals and people.
"I think it's likely to be true that other areas of the brain, higher areas of the brain, have their critical (developmental) periods later in life," said the study's senior author Michael P. Stryker, Ph.D.", and some of them, in the highest areas, the critical periods never close until senility."
What's more, the amount of plasticity (connections between nerve cells) in the brain depends on the amount of deep sleep, which is indicated by large slow brain waves. This is the sleep that a person falls into when they first go to sleep, and accounts for half of sleep time in young animals and human babies, (who get up to three times more sleep than adults). Stryker said this is precisely the time in life when the brain reorganizes its connections to attain the perfect precision it needs as an adult.
Better Way to Prepare for Exams
Sleep could prove to be an important part of the strategy for preparing for challenges such as exams. "The fact that sleep provoked slightly more plasticity (connections between nerve cells) than double the amount of exposure to experience - suggests that if you reviewed your notes thoroughly until you were tired and then slept, you'd achieve as much plasticity, or 'learning,' in the brain as if you'd pulled an all-nighter repeating your review of the material," says Michael P. Stryker, Ph.D., researcher at the University of California, San Francisco studies have shown that sleep-loss affects learning and memory. When animals and humans are deprived of sleep, they do not perform well on memory tasks.
REM Sleep Enhances Emotional Memory-Study
Human research supports the function of rapid eye movement (REM) sleep in memory formation. German scientists at the University Of Bamberg Department Of Physiological Psychology compared memory retention of emotional versus neutral text material. Participants were tested over intervals covering either early sleep (dominated by slow wave sleep) or late sleep when REM sleep is dominant.
Sleep not only improved retention, compared to a wake group, but "late sleep particularly enhanced memory for emotional texts. This effect was highly significant in comparison with memory for neutral texts," said the authors. "Results are consonant with a supportive function of REM sleep predominating late sleep for the formation of emotional memory in humans."
REM Sleep and Learning-Study
After reviewing the existing research on sleep, dreams, learning, and memory, Dr. Robert Stickgold and his colleagues at Harvard Medical School concluded that REM sleep seems to be essential for learning how to do things. Learning to play a musical instrument is an example of such "procedural learning."
Decision-making also appears to benefit from this overnight form of cogitation. During sleep, particularly the REM phase, the brain integrates information it took in during the day but couldn't process at the time. "Sleeping on it" is not necessary, however, for simple memory or learning tasks. Dr. Stickgold also believes that sleep may be involved in "erasing memories from the immediate and distant past," and that dreaming is probably a piece of this process.
Activating Memory in Sleep-Study
Earlier studies with rodents, birds, and humans have suggested that brain activity initiated while awake is later reactivated during subsequent sleep, as part of the process that consolidates recent experience into memory. Scientists at Rockefeller University showed that, in rats, certain brain cells that activate during daytime exploration tend to reactivate during sleep. Sidarta Ribeiro, Constantine Pavlides, and colleagues found that exposure to a "memorable" environment causes the brain to turn on a gene called zif-268 that is associated with strengthened communication between nerve cells.
The researchers exposed a group of rats to novel, enriched environments (labyrinths with toys), and another group of rats to their normal home cages. Then the rats went to sleep, passing through successive stages of slow wave and REM sleep.
During slow wave sleep, zif-268 turned off in all rats, regardless of which environment they had experienced. But during REM sleep, zif-268 turned on in the cerebral cortex and hippocampus of only rats that had explored the labyrinths. The gene stayed off in rats that had not experienced the enriched environments.
This retrieval of zif-268 activity during REM sleep may couple with other reactivated brain mechanisms to "process" memories of novel experiences. Such processing may in turn prove important for cementing the memories acquired while awake.
Napping-Study
Why do cats nap? Because they can, but so can you. Simply taking a nap may be one of the best things you can do to correct poor mental performance, especially after a stressful night of disrupted sleep, such as from sleep apnea or snoring . Naps can help make-up for nighttime loss.
In a study of Japanese men, a mid-afternoon nap had positive effects upon the maintenance of their daytime vigilance level. The 20-minute nap improved performance level and their self-confidence.
EXERCISING EVERYDAY A BOON TO OSTEOARTHRITIS PATIENTS
Adherence to Recommended Exercise Improves Physical Function, Reduces Pain for Osteoarthritis Patients.
ScienceDaily (July 27, 2010)
Patients with osteoarthritis (OA) of the knee or hip who adhere to the recommended home physical therapy exercises and physically active lifestyle experience more improvement in pain, physical function, and self-perceived effect according to a study from researchers in the Netherlands. Research also shows that maintenance of exercise behavior and physically active lifestyle after discharge of physical therapy improves the long-term effectiveness of exercise therapy in patients with knee or hip OA.
Details of the study are available online and will publish in the August print issue of Arthritis Care & Research, a journal of the American College of Rheumatology.
Individuals with OA of the hip or knee experience pain, reduced muscle strength, decreased range of joint motion, and joint instability. According to the World Health Organization (WHO) OA is one of the ten most disabling diseases in developed countries. Further WHO estimates state that 80% of those with OA have limitations in movement, and 25% cannot perform major daily life activities. Often OA patients are referred to physical therapy in order to reduce impairments and improve overall physical function to meet demands of daily living. Although exercise therapy has beneficial short-term effects, earlier research has shown that after discharge of exercise therapy the positive treatment effects decline over time and finally disappear in the long-term.
The Dutch research team conducted an observational follow-up study on 150 patients with OA of the hip and/or knee who were receiving exercise therapy. The study subjects were followed for 60 months to assess adherence to self-directed exercise (during and after prescribed physical therapy treatment period) on patient outcomes of pain, physical function, and self-perceived effect. Three forms of adherence, which is defined as the subject's behavior that corresponds to agreed recommendations by his or her physical therapist, were measured-adherence to home exercises, home activities, and increased physical activity. Researchers used a self-report questionnaire to measure participants' adherence to home exercise (e.g. muscle strengthening exercises) and activity (e.g. walking or cycling). Assessment of adherence started at baseline, and then took place again at 3, 15, and 60 months.
Patient outcomes of pain and physical function were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. The WOMAC scale ranges from best to worst, meaning lower scores represent less pain and improved physical function. Participants' physical performance was measured by the time (in seconds) it took to walk the distance of 5 meters with improvement in performance noted by a reduction in time to complete the walk.
Results show at the 3-month follow-up 57.8% of study subjects adhered to the recommended exercises and 53.8% to recommended activities. Adherence to exercise was significantly associated with a decrease in pain (-1.0 points on a scale from 0 to 20), and improvements in self-reported physical function (-2.3 points on a scale from 0 to 68) and physical performance (-0.29 seconds compared with the base-line time of 4.8 seconds to walk 5 meters (16 feet)). "Better adherence to home exercises and being more physically active improves the long-term effectiveness of exercise therapy in patients with OA of the hip and/or knee," said lead study author, Martijn Pisters, M.Sc., PT.
A higher level of moderate or vigorous intensity physical activity was significantly associated with a decrease in pain, physical function and physical performance, as well as a positive self-perceived effect. The authors found that one hour per week more of physical activity at a moderate level resulted in an improvement in self-reported physical function of -0.24 on a scale from 0 to 68. During the physical therapy treatment period, the patients' physical activity increased by 1.5 hours of moderate or vigorous intensity physical activity per week. After the treatment period, physical activity declined by 0.5 and 1.3 hours respectively at the 15 - and 60-month follow-up.
Additionally, researchers noted a decline in exercise adherence upon completion of physical therapy with only 44.1% of patients and 30.1% still exercising at the 15 - and 60-month follow-up, respectively. Similarly, adherence to home activities decreased at the 15- and 60-month follow-up with only with 29.5% and 36%, respectively, of study subjects being adherent. "Future research should focus on how exercise behavior can be stimulated and maintained in the long term to improve outcomes for patients with OA," concluded Mr. Pisters.
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Wiley - Blackwell, via AlphaGalileo.
Journal Reference:
Martijn F Pisters, Cindy Veenhof, François G Schellevis, Jos WR Twisk, Joost Dekker, Dinny H De Bakker. Exercise adherence improves long-term patient outcome in patients with osteoarthritis of the hip and/or knee. Arthritis Care & Research, 2010; DOI: 10.1002/acr.20182
GENE LINKED TO BREATHING DISORDERS
CLEVELAND, Sept. 3, 1996 -- One of the miracles of life is a newborn's ability to begin breathing on its own. Now scientists at Case Western Reserve University School of Medicine report a major advance in understanding the postnatal development of normal breathing behavior, as well as how this process can become fatally impaired. The researchers have shown that a naturally-occurring, hormone-like molecule, called Brain-Derived Neurotrophic Factor (BDNF), is required for the development of normal breathing after birth.
Using genetically engineered mice, the scientists found that animals lacking BDNF were missing a specific group of nerve cells critical for the control of respiration and displayed severely abnormal breathing responses to various environmental conditions. The breathing abnormalities were associated in particular with an inability to sense changes in blood oxygen levels. BDNF-deficient mice die within two to three weeks after birth, and it now appears likely that the animals' premature death is linked to their breathing difficulties.
According to David M. Katz, Ph.D., associate professor of neurosciences and leader of the research team, "The findings are significant because they establish a link between a gene required for nervous system development and a specific disorder of breathing in mice. Particularly intriguing are possible relationships between the mechanisms underlying abnormal breathing in the mutant mice and disorders such as Sudden Infant Death Syndrome, sleep apnea, and Congenital Chronic Hypoventilation Syndrome (Ondine's Curse) in human patients."
According to James P. Kiley, Ph.D., director of the Airway Biology and Disease Program of the National Heart, Lung, and Blood Institute, "Identifying genetic factors responsible for specific respiratory defects is an important area of research since such studies contribute significantly to fundamental knowledge of genetic based defects and respiratory control mechanisms in health and disease."
An infant's inability to sense or respond to dangerously low oxygen or high carbon dioxide levels may play a role in Sudden Infant Death Syndrome (SIDS), one of the commonest forms of death in apparently healthy children between two and six months of age. In premature infants, impaired responses to low oxygen levels may predispose them to prolonged periods of respiratory arrest, termed "apnea of prematurity," which can in turn derange normal development.
Even more common is adult sleep apnea, a condition affecting approximately 12 million Americans, in which the ability to "sense" abnormal breathing is thought to be important in arousing a person from potentially life-threatening episodes of airway obstruction. Recent studies in humans, carried out by Susan Redline, M.D. and her colleagues, also at Case Western Reserve University School of Medicine, have demonstrated a familial association between SIDS, sleep apnea and impaired responses to low oxygen, raising the possibility that these conditions share a common underlying mechanism.
"Although our results are just a first step, it is possible to imagine one day using a molecule such as BDNF to augment maturation or functioning of the oxygen sensing system and thereby treat disorders of breathing in human patients," said Dr. Katz.
The research, which is supported by the National Heart, Lung and Blood Institute of the National Institutes of Health and the Francis Families Foundation, was carried out by a post-doctoral fellow in Dr. Katz's laboratory, Dr. Jeffery Erickson, in collaboration with scientists at the Centre Nationale des Recherches Scientifiques (Gif-sur-Yvette, France), Regeneron Pharmaceuticals, Inc. (Tarrytown, NY) and Bristol-Myers Squibb (Princeton, NJ). The mice carrying the BDNF gene deletion were produced at Regeneron by a research team headed by George D. Yancopoulos, M.D., Ph.D., Regeneron's vice president, Discovery. Regeneron is collaborating with Amgen Inc. and Sumitomo Pharmaceuticals Company, Ltd. on BDNF development. Dr. Yancopoulos commented that "the work of Dr. Katz and his colleagues may lead to new treatment possibilities for patients with breathing disorders." The study appears in the September 1, 1996 issue of the Journal of Neuroscience, the official journal of the Society for Neuroscience.
SOLUBLE FIBER IN OATS, APPLES AND NUTS REDUCES INFLAMMATION AND STRENGTHENS IMMUNE SYSTEM
A new University of Illinois study touts the benefits of soluble fiber-found in oats, apples, and nuts, for starters-saying that it reduces the inflammation associated with obesity-related diseases and strengthens the immune system.
"Soluble fiber changes the personality of immune cells-they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection," said Gregory Freund, a professor in the University of Illinois's College of Medicine and a faculty member in the College of Agriculture, Consumer and Environmental Sciences' Division of Nutritional Sciences.
This happens because soluble fiber causes increased production of an anti-inflammatory protein called interleukin-4, he said.
The study will appear in the May 2010 issue of Brain, Behavior, and Immunity and is available online at ttp://www.sciencedirect.com/science/journal/08891591.
In the experiment, laboratory mice consumed low-fat diets that were identical except that they contained either soluble or insoluble fiber. After six weeks on the diet, the animals had distinctly different responses when the scientists induced illness by introducing a substance (lipopolysaccharide) that causes the body to mimic a bacterial infection.
"Two hours after lipopolysaccharide injection, the mice fed soluble fiber were only half as sick as the other group, and they recovered 50 percent sooner. And the differences between the groups continued to be pronounced all the way out to 24 hours," said Christina Sherry, who also worked on the study.
"In only six weeks, these animals had profound, positive changes in their immune systems," she said.
Now Freund has a new question: Could soluble fiber offset some of the negative effects of a high-fat diet, essentially immunizing obese persons against the harmful effects of fat?
Scientists have long known that obesity is linked to inflammatory conditions, such as diabetes and heart disease.
Yet, in a recent study, the University of Illinois scientists demonstrated that fat tissue produces hormones that appear to compensate for this inflammation. "There are significant anti-inflammatory components in fat tissue and, if they were strategically unleashed, they could potentially protect obese people from further inflammatory insults, such as a heart attack or stroke. In obese animals, you can see the body compensating in an effort to protect itself," he said.
Not all fat is bad, the researcher noted. The Mediterranean diet, which receives high marks for its health benefits, includes such foods as olive oil; salmon, tuna, sardines, and trout, which contain important omega-3 and - 6 fatty acids; and plant sources of fat, such as flaxseed.
"Now we'd like to find a way to keep some of the anti-inflammatory, positive effects that develop over time with a high-fat diet while reducing that diet's negative effects, such as high blood glucose and high triglycerides. It's possible that supplementing a high-fat diet with soluble fiber could do that, even delaying the onset of diabetes," he said.
This study is one of the first to provide two valuable lessons, said Sherry. The first, already noted, is that soluble fiber has direct anti-inflammatory effects and builds up the immune system. The second is that the amount of soluble fiber necessary to achieve these health benefits is a reasonable, not a pharmacological, amount.
The recommended daily dietary recommendation is 28 to 35 grams of total fiber, but most of the FDA's health claims are for insoluble fiber, and that's where things get a bit complicated, she said.
"Not all fiber is created equal, although you wouldn't know that by reading nutrition labels," said Sherry. "Most manufacturers don't tell you how much of each type of fiber a food contains, and we think it's important that this information be included on a product's packaging."
Good sources of soluble fiber are oat bran, barley, nuts, seeds, lentils, citrus fruits, apples, strawberries, and carrots. "We used a citrus-based pectin in our study," Sherry said.
Insoluble fiber, found in whole wheat and whole-grain products, wheat bran, and green, leafy vegetables, is also valuable for providing bulk and helping food move through the digestive system, but it doesn't provide the boost to the immune system that soluble fiber provides.
Source: University of Illinois at Urbana-Champaign
IMMUNIZATION
Development of new vaccines
A number of new vaccines with major potential for controlling infectious diseases have just been licensed or are at advanced stages of development. Among the illnesses targeted are rotavirus diarrhea, pneumococcal disease, and cervical cancer (as caused by human papillomavirus), which together kill more than a million people each year, most of them in developing countries. In addition to these efforts against diseases of global importance, progress is being made on a vaccine for the regional menace posed by meningococcal meningitis serogroup A, which causes frequent epidemics and high rates of death and disability in African countries south of the Sahara.
These advanced candidate vaccines are the focus of the information provided below. However, it should be noted that continuing, intensive efforts are under way to develop effective vaccines for AIDS, malaria, tuberculosis, dengue, leishmaniasis, and enteric diseases, among others and to adapt new technologies to improved formulation and delivery.
Vaccine development proceeds through discovery, process engineering, toxicology and animal studies to human Phase I, II, and III trials. The process can take more than 10 years, depending on the disease. The human trials focus initially on safety, involving small groups of people (I); then progress to moderate-sized "target" populations (persons close to the age and other characteristics for whom the vaccine is intended) to determine both safety and the stimulation of immune response (II); and finally to large target populations to establish whether a vaccine actually prevents a disease as intended (efficacy) (III).
The current situation of a number of new vaccines is described below:
Rotavirus
Acute diarrhea is responsible for nearly 1.9 million deaths per year in children under age five. Rotavirus is responsible for as much as one fourth of these casualties, almost all of which occur in developing countries.
Status of vaccine development: RotaRix, a vaccine developed by GlaxoSmithKline (GSK), against rotavirus diarrhea is now licensed in many countries. In addition to being available on the private market in these countries, it has now been introduced in the public sector immunization programs of Brazil, El Salvador, Mexico, Panama and Venezuela. A Phase III trial is also under way in South Africa and Malawi.
RotaTeq, a rotavirus diarrhea vaccine developed by Merck, is licensed and has been introduced in the immunization program of Nicaragua. Trials in Asia and Africa are likely to start in 2007. Rotavirus vaccines in earlier stages of development include a vaccine sponsored by the United States National Institutes of Health; a neonatal vaccine developed by an Indian-United States consortium; and an Australian neonatal vaccine. They may provide an alternative option to today's products.
Challenges: A vaccine must be effective against numerous rotavirus strains (serotypes), including those prominent in developing countries. Large, stringent safety trials are necessary because an earlier, unrelated rotavirus vaccine appeared to cause, in rare cases, a serious complication called intussusception, a reverse telescoping of one part of the intestine into another. These vaccines, since they are live, oral ones, must be shown not to interfere with oral polio vaccine and must be efficacious. Even more importantly, they must be shown to be safe in general, and in HIV-infected children in particular. Price will also be an issue for large-scale introduction.
Prospects: Rotavirus vaccines are starting to be used in developing countries, but information on their effectiveness in Africa and Asia will not be available until 2008. They are expected to be ready for widespread use in immunization programs in Africa and Asia by 2009.
Pneumococcal disease
Acute lower respiratory infections are responsible for close to two million deaths per year and a large proportion of these are caused by Streptococcus pneumoniae (pneumococcus). A study in The Gambia has indicated that more than one third of these deaths might be caused by pneumococcus. Most victims are children in developing countries. Pneumococcus also causes other serious illnesses such as meningitis and septicaemia. Pneumonia deaths far outnumber deaths from meningitis. Nonetheless, in non-epidemic situations, Streptococcus pneumoniae is a major cause of meningitis fatalities in sub-Saharan Africa; of those who develop pneumococcal meningitis, 40-75 % either die or are permanently disabled. Children infected with HIV/AIDS are 20-40 times more likely to contract pneumococcal disease than children without HIV/AIDS.
Status of vaccine development: A seven-valent conjugate vaccine called Prevnar (or Prevenar) is designed to act against seven strains of pneumococcal disease. It has been developed by Wyeth Vaccines and is licensed in the United States and over 70 other countries, but does not include two serotypes (types 1 and 5) that cause a high percentage of pneumococcal illness in developing countries. (Conjugate vaccines, which have proven to be highly effective, are made by linking purified polysaccharides - complex sugars - from the coat of a disease-causing bacterium to a protein "carrier.") In the United States, use of this vaccine has led to a dramatic decline in rates of pneumococcal disease, not only in immunized children, but also in the un-immunized population through reduced transmission. Wyeth Vaccines has also completed evaluation of a nine-valent conjugate vaccine, including serotypes 1 and 5. A Phase III trial of the vaccine involving 40 000 people was completed in South Africa in 2002, and a Phase III trial with 17 437 subjects was concluded in the Gambia in 2004. In the South African trial, the vaccine reduced invasive disease caused by the relevant serotypes by 83% in HIV-uninfected children and by 65% in HIV-infected children. Results from The Gambia trial show the vaccine was 77% effective in preventing infections caused by the relevant serotypes; that it resulted in 37% fewer cases of pneumonia (as confirmed by chest X-ray) as compared with a control group; and that recipients experienced a 16% reduction in overall mortality. Vaccines containing ten or thirteen serotypes are expected to be submitted for licensure within the next few years. In addition, developing country vaccine manufacturers have initiated development of conjugate vaccines. Vaccines based on common protein antigens of pneumococcus are also in the pipeline.
Challenges: It can be difficult to establish the extent of pneumococcal disease as developing countries often lack the laboratory facilities, expertise, and resources to do so. As a result, public health decision-makers are often unaware of the prevalence of the disease and of the toll it exacts in death and disability. Because of the scarcity of data from developing countries, there is concern over the appropriate serotype valency for developing countries. Concerns remain - although results to date are encouraging - that prevention of some serotypes of pneumococcal disease may be offset by an increase in incidence of disease due to other serotypes. The price of the vaccine, although still to be set for developing countries, may be too high for them to afford without special financing arrangements. A new innovative financial initiative (AMC - Advanced Market Commitment) may soon provide financing for the purchase of pneumococcal vaccine.
Prospects: A vaccine providing effective protection against pneumococcal disease for young children in developing countries could be introduced in a few countries, provided adequate supply and financial help are arranged.
Human papillomavirus (HPV)
Sexually transmitted HPV is the major cause of cervical cancer, the most common cause of cancer deaths among women in developing countries. About 500 000 cases occur each year, 80% of them in developing countries. Cervical cancer kills some 240 000 women annually.
Status of vaccine development: Gardasil, an HPV vaccine recently licensed by Merck, covers four types of HPV, including the cancer-causing types 16 and 18 and types 6 and 11 for non-cancerous genital warts. A second vaccine, developed by GSK, covers HPV types 16 and 18 alone and is expected to be licensed in 2007.
Challenges: HPV types 16 and 18 cause around 70% of HPV cervical cancers globally, but the vaccines in development will not cover the 30% of cancers attributed to other HPV types. Because these other types are numerous and individually only contribute a small percentage, significantly expanding vaccine coverage against them may present technical challenges for manufacturers. The duration of the immunity conferred by the vaccines is not yet known, and only time and follow up studies will provide this critical information. Other clinical studies are planned that will look at alternative schedules and possibly lowering the age of vaccination. Because HPV is spread by sexual contact, and the high-risk years for infection are roughly from ages 18 to 25, the best subjects for vaccination will likely be pre-adolescents or adolescents, unlike for traditional vaccination programmes, which are aimed mostly at infants and pregnant women. Access to the vaccines is likely to be an issue in developing countries due to limited resources for the implementation of vaccination programmes.
Prospects: Discussions are ongoing about collecting the necessary data for introducing the vaccines into developing countries. Their systematic use in developing countries may well depend on local epidemiology, acceptability, financial resources, and the feasibility of vaccinating adolescents. There is also an immediate need to put in place an information/communication strategy, at all levels and for WHO to develop a position on the future use of this vaccine and the related public health opportunities it can offer.
Meningococcal meningitis A (Men A)
The African "meningitis belt" - which includes all or part of 21 countries stretching south of the Sahara desert from Senegal to Ethiopia - is the site of frequent epidemics, usually caused by serogroup A meningitis. Over the past decade more than 700 000 cases have been reported. Roughly 10-20 % of persons infected die, and one out of five survivors is likely to suffer from a permanent disability such as hearing loss, mental retardation, or paralysis. The rate of meningitis epidemics in the region has increased in recent years.
Status of vaccine development: Polysaccharide vaccines (vaccines made from complex sugars taken from the outer coats of the Men bacterium) are currently in use, but are not very effective at protecting young children, do not create long-lasting immunity, and do not confer a "herd effect" - that is, do not prevent spread of the disease in non-vaccinated people through reduction of the carriage of the infectious agent by vaccinated people during epidemics. Because of these shortcomings, immunization with polysaccharide vaccines is usually undertaken only after the onset of an epidemic.
To provide greater and more efficient protection, a public-private effort called the Meningitis Vaccine Project (MVP) is developing a Men A conjugate vaccine. This vaccine is intended to have long-lasting effect, to create immunity in infants, and to allow protection to be conferred in advance through mass immunization programmes. Toxicology studies and animal studies have been successfully completed, and the animal studies suggest the conjugate vaccine is highly immunogenic - that is, stimulates high levels of antibodies against Men A infection. Phase I trials were conducted in India and Phase II trials are ongoing in Mali and The Gambia. Recruitment has been completed and preliminary results are expected in early 2007. Phase II and III trials are being prepared in the same sites, in addition to in Ethiopia and Senegal. A Phase II infant study is planned in Ghana.
Other conjugate vaccines, including a heptavalent vaccine (DTP Hep B Hib) covering serogroups A, and C, are being developed by the private sector; and a tetravalent vaccine has recently been licensed by Sanofi-Pasteur in the United States and Canada.
Challenges: Other meningococcal meningitis strains are circulating in Africa which will not be controlled by a vaccine for serogroup A. One strain, referred to as W135, has caused epidemics in Burkina Faso and a small outbreak serogroup X has recently been reported in Nigeri. This points out to the continued need for an strengthened surveillance in the countries of the meningitis belt.
Prospects: A low-priced (around US$ 0.40 per dose) conjugate vaccine for Men A may be ready for widespread use in the African meningitis belt by 2008 or 2009. In the meantime, sustainable funding, programmatic and delivery mechanisms need to be put in place in the belt countries to prepare the introduction and future use. A heptavalent vaccine will also be available (expected price US$ 4.50 per dose) in the same time frame,; it will protect against diphtheria, tetanus, pertussis, hepatitis B,Haemophilus influenzae type B and meningitis serogroups A and C.
WHO Initiative for Vaccine Research (IVR)
The WHO Initiative for Vaccine Research was established in 2001 to streamline the various vaccine research and development projects being carried out by different departments of WHO (including the Special Program for Research and Training in Tropical Diseases: TDR) and UNAIDS. IVR is an international team of scientists, managers, and technical experts whose task is to facilitate the development of vaccines against infectious diseases of major public health importance, to improve existing immunization technologies, and to ensure that these advances are made available to the people who need them the most. IVR will achieve these objectives using a three-pronged approach:
- Management of knowledge and provision of guidance and advocacy through effective partnerships to accelerate innovation for new and improved vaccines and technologies;
- Support to research and product development for WHO priority new vaccines and technologies; and
- Conduct of appropriate implementation research and development of tools to support evidence-based recommendations, policies and strategies for optimal use of vaccines and technologies.
