Meningitis vaccine guidelines

Two types of meningococcal vaccines are currently used to prevent the infection that causes meningitis: meningococcal polysaccharide vaccine (MPSV4) and meningococcal conjugate vaccine (MCV4). Particular high-risk groups should be immunized according to CDC guidelines.

Read an overview of meningococcal vaccination and booster guidelines

Should I delay pneumococcal conjugate vaccine?

The pneumococcal conjugate vaccine is used in infants and young children to prevent infections by the bacteria Streptococcus pneumoniae. The vaccine contains inactivated or killed bacteria to stimulate the immune system against it. In 2000, the US Food and Drug Administration (FDA) licensed a 7-valent (protects against 7 serotypes of the bacteria) vaccine (PCV7), but this was replaced in 2010 with a 13-valent vaccine (PCV13), allowing greater protection. PCV13 is administered to children from 6 weeks up to 71 months according to the Centers for Disease Control (CDC). 

Traditionally, the pneumococcal conjugate vaccine was outlined for use by the National Institutes of Health (NIH) in children aged between 2 and 15 months, though the last booster could be up to 59 months. A different vaccine, pneumococcal polysaccharide vaccine (PPV23), is given to older children and adults because children under the age of 2 cannot mount the T cell response required. However, vaccination with PCV13 may be delayed for a number of different reasons.

Why vaccinate against pneumococcus?

In 2006, the World Health Organization (WHO) published a detailed review on pneumococcal infections and vaccination. According to the WHO review, 10 serotypes of pneumococcus are responsible for invasive pediatric infections, though 20 serotypes are responsible for infections in all age groups worldwide. Streptococcus pneumoniae usually colonizes the nasopharynx (the cavity behind the nose and above the throat). It typically does not cause infection or symptoms. However, when the bacteria spread to the ear or sinuses, or are aspirated into the lungs, it can cause an infection.

After the introduction of PCV7, the number of invasive infections decreased 80 percent, decreasing complications and death along with it. However, in 2006, the WHO pointed out that more than 1.5 million people, half of them under the age of 5 years, still die each year due to pneumococcal infection. Invasive S. pneumoniae causes pneumonia, meningitis, and blood infection, which are all serious diseases. Young age is a specific risk factor for pneumococcal infection, and one-quarter to one-half of pneumococcal meningitis survivors have long-term neurological disease. In addition, the antibiotics used to treat infection are becoming less and less useful due to bacterial resistance to treatment. Approximately 10 percent of infected children die according to the CDC.

Vaccination against the bacteria reduces the risk of invasive disease. It prevents pneumococcus-associated ear infections, pneumococcus-associated meningitis and long-term neurological damage and, most importantly, pneumococcus-related death. Young children are vaccinated because they are the population most at risk, though the elderly and HIV patients are also at-risk populations. The 2006 WHO review indicated that vaccinating children benefitted all age groups in the form of decreased disease.

Reasons for not vaccinating

Though most children can go into a pediatrician’s office or health department and get a vaccine without additional considerations, there are times when a vaccine should not be given. Pneumococcal conjugate vaccine may be delayed if the child has a current infection or illness more serious than a cold. Once they have recovered, they may be vaccinated. Some healthcare providers may choose to administer PCV13 separately from Hib vaccine due to potentially decreased efficacy, though the WHO does not find support for the practice.

Pneumococcal conjugate vaccine may be withheld (not given at all) when the child simply cannot tolerate it, such as in the case of a previous allergic reaction to any component of PCV7 or PCV13 or any vaccine containing diphtheria toxoid (DTaP). In addition, the WHO recommends that anyone who has already received PPV23 not receive PCV7 (and by equivalence PCV13).

Standard practice

Most children can and should be vaccinated with pneumococcal conjugate vaccine. Any exceptions can be discussed with your pediatrician.

Coming to a town near you: Whooping cough

Australia is seeing a surge in whooping cough cases. So much so that they've released the vaccine for free! California is also requiring teen vaccinations in light of recent whooping cough deaths.

Whooping cough is a respiratory infection caused by a Gram-negative bacterium called Bordetella pertussis. Pertussis is endemic to the United States, with epidemics occurring every 3-5 years and with an average 5000-7000 cases per year. However, since the 1980s, the incidence of whooping cough has increased, with more than 10,450 cases reported in 2007. The last major outbreak occurred in 2005, with more than 25,000 cases. Health officials are hoping to prevent another such outbreak.

Since the 1990s, cases have disproportionately increased in older children and young adults, likely because of anti-vaccine momentum among their parents and possibly evolution of the bacterium itself.

Infants and young children are particularly prone to respiratory and neurological complications from the infection, and deaths are more common among unvaccinated children or those who are too young to be vaccinated. The disease is highly contagious, with 90% of contacts with an infected individual becoming infected themselves. Since the 1990s, cases have disproportionately increased in older children and young adults, likely because of anti-vaccine momentum among their parents and possibly evolution of the bacterium itself.

One challenge to decreasing the incidence of whooping cough in the U.S. is to increase vaccine (DTaP) and booster (Tdap) coverage among both children and adults. The vaccine for pertussis is given in conjunction with the vaccines for diphtheria and tetanus. There are also variations and lower strength doses (such as the booster) for children who cannot tolerate the pertussis vaccine. Children generally get five doses of DTaP (containing full strength dose of pertussis toxin protein): 2, 4, 6, and 15-18 months old and again at 4-6 years of age. A booster (low dose, Tdap) is recommended for adolescents around the age of 11-12 years. The pertussis component can be given in conjunction with a regular tetanus booster (Td) in a single injection. The anti-vaccine movement has raised parents’ fears about a number of disorders being associated with pediatric vaccines, from autism to SIDS, but no medical evidence exists to substantiate these fears.

From 1990-1993, the coverage of the third DTaP dose decreased in the United States to below 90%, even below 85% in 1992. Though it increased back to the mid 90 percent range, it has remained lower than the coverage in the 1980s. A child’s immune system does not develop until roughly 9 months of age, making the third and later doses critical to their long-term immunity against whooping cough. The bacterium can be transmitted to others even before the distinctive cough sets in, making transmission among adults and adolescents who did not receive all of their doses as children highly likely.

Other factors that have led to increased incidence of whooping cough in the U.S. is an adaptation of the pertussis bacteria to survive in vaccinated individuals. The exact mechanism of this adaptation is not clear, possibly linked to the decreased vaccination coverage or adaptation to the immune response, or possibly genetic drift and decreased vaccine efficacy. The vaccine is being updated from a whole cell formulation to an acellular formulation to avoid side effects among some children, but further improvements in the components of the vaccine may be necessary to have an effect on new strains of the pathogen.

Broadly neutralizing HIV antibodies and the hope for a vaccine

Antibody binding HIV. Peter Kwong, NIH

Yesterday I posted about how HIV antibodies are made. But why are they important? More specifically - why is the recent work on broadly neutralizing antibodies important?

Antibodies are produced against cell surface proteins, the portions of the infecting agent visible to immune cells. The problem thus far with HIV is the broad range of cell surface proteins expressed by the various strains currently infecting the human population, as well as the potential mutations to come. However, broadly neutralizing antibodies, though rare, have been identified in the blood of HIV-infected patients. They bind and affect portions of the cell surface that remain relatively constant among HIV strains.

Read more about the challenges and promise of broadly neutralizing antibodies in HIV vaccine development below the break.

 

 

 

HIV antibody production

To exploit the immune response and the natural system of neutralizing or killing a virus and preventing infection, researchers develop antigens that stimulate the human body to make the antibodies that are most efficient and effective at achieving the intended goals.

For HIV, though, this has been difficult because the surface antigens of HIV vary broadly among infected individuals. A solution to this problem is thought to exist with broadly neutralizing antibodies, naturally occurring human antibodies against relatively constant antigens on the surface of the HIV virion.

When a pathogen or foreign agent enters the human body, the immune system responds in both a broad and specific manner. The human immunodeficiency virus (HIV), the pathogen that causes AIDS, is no exception. The specific immune response involves the processing of the pathogen and presentation of its proteins, or antigens, by specialized immune cells (macrophages and dendritic cells) to other immune cells, one type of which, specifically B cells, are then activated to genetically rearrange and produce antibodies specific to the viral proteins. Antibodies are simply specialized proteins that are produced on an as needed basis under normal circumstances. When an antibody comes into contact with an antigen, usually on the cell or pathogen surface because of accessibility, it binds and causes the pathogen to either be neutralized or destroyed.

Vaccines are a method of artificially stimulating antibody production by exposing the immune system to antigens prior to infection. The human body produces antibodies specific to the antigens or strain with which it is infected. For HIV, this specificity makes vaccination thus far troublesome as the surface antigens of HIV vary broadly among infected individuals. A solution to this problem is thought to exist with broadly neutralizing antibodies, naturally occurring human antibodies against relatively constant antigens on the surface of the HIV virion. These consistent proteins are involved in the infectivity of HIV – the CD4 binding site (glycoprotein gp120) that allows the virus to bind T cells and gp41, the surface protein involved in HIV envelope and cell membrane fusion and viral entry.

To exploit the immune response and this natural system of neutralizing HIV and preventing infection, researchers develop antigens that stimulate the human body to make the antibodies that are most efficient and effective at achieving the intended goals. The most promising method of making HIV antibody is thought to involve creating a vaccine with components that mimic the HIV glycoproteins involved in CD4 recognition and binding – corresponding to the broadly neutralizing antibodies VRC01 and VRC02, which are reported to prevent 90 percent of global HIV strains from infecting human cells in the lab (work by the NIH). The previous most promising vaccine candidate was found in clinical trials to only benefit less than one-third of individuals, which does not meet the goals of vaccination. The discovery of the VRC antibodies is hoped to further advance work on a vaccine that will stimulate the human body to make HIV antibody effectively and in a manner that prevents infection with most, if not all, strains of the virus.

Profile: International AIDS Vaccine Initiative

The International AIDS Vaccine Initiative (IAVI) is a global nonprofit organization comprising three consortia of HIV/AIDS researchers: the Neutralizing Antibody Consortium (NAC), the HIV Live-attenuated Consortium, and the Vectors Consortium. The mission of the Initiative according to the IAVI website is to “ensure the development of preventive AIDS vaccines that are not only safe and effective, but also accessible to all people”. The consortia work with more than 50 academic, government, and private institutions and have so far tested nine vaccine candidates in 11 countries, concentrating on strains present in the developing world, as they account for 95 percent of new infections.

In 2006, the Initiative celebrated 10 years, releasing a timeline of its growth during that time: IAVI was founded in 1996 in response to the global need for an HIV vaccine and other methods to curb the spread of AIDS outlined in a 1994 conference held by the Rockefeller Foundation. The initial funding support was from notable charitable and humanitarian organizations: the Rockefeller, Starr, and Alfred P. Sloan Foundations, Foundation Merieux, Until There’s  a Cure, and the World Bank. The initiative also garnered support from the Joint United Nations Programme on HIV/AIDS (UNAIDS). Later support came from European governments and joint ventures were pursued with the National AIDS Trust. In 1998, IAVI released its “Scientific Blueprint for AIDS Vaccine Development”. The initiative is now funded by both private and public institutions, non-governmental organizations (NGOs), governments, and community groups.

In 2009, the AIDS vaccine community had proof-of concept success in Thailand, showing that a combinatorial vaccine was able to prevent 30% of HIV infections. Though this was not a success per se, it was a small step toward proving that their work is not fruitless. The research community made additional progress in 2010 with broadly neutralizing antibody research, the focus of one of its consortia. The antibodies identified by NAC in 2009 have been taken up by other research groups in the National Institutes of Health (NIH) who may have found a model antibody for preventing more than 90% of HIV infections, the best vaccine candidate to date.

The goal of a vaccine is to prevent new infections. Since AIDS emerged in the 1980s, 30 million deaths have been attributed to the syndrome, and UNAIDS estimates from numbers released in 2010 that more than 33 million people are currently living with HIV, the AIDS virus. The virus attacks cells of the immune system, leading to a state of immunodeficiency. This state allows opportunistic infections to wreak havoc and kill the infected individual, the syndrome known as AIDS. Despite decreased infections rates due to educational campaigns regarding safe sex and needle sharing, it is estimated that nearly 7100 people are infected with HIV each day. More than half of all infections occur in Sub-Saharan Africa, a region that also accounted for three-fourths of all AIDS-related deaths in 2008. Yet, the infection rates are also increasing in more developed countries, including China, Germany, Britain, and Australia. The lack of control of the epidemic over nearly three decades re-emphasizes the need for a vaccine and other more global preventative measures.

The next possible AIDS vaccine

NewScientist is reporting that research from the Children's Hospital of Philadelphia has found an alternative vaccine method for preventing HIV infection. Using a virus to produce antibodies in the muscle - bypassing the immune system altogether and avoiding the cells that HIV infects.

They followed up on 9 macaques who were vaccinated and then exposed to SIV (the simian AIDS virus) over 85 weeks (roughly a year and half). None have been found to be infected. The control group was not vaccinated but exposed to SIV - 4 of the 6 monkeys have died of simian AIDS.

They hope that it makes it to the clinic, adjusted for HIV as opposed to SIV, in 2-3 years.

The issues I foresee being potential downfalls are:

• The length of protection by the injection - how long are the antibodies produced? How often is re-injection needed? How long does protection last (do the antibodies remain or are they transient)? It uses gene insertion, but as foreign DNA is it accepted indefinitely?
• The specificity of the antibodies for HIV as opposed to a less specific response (possibly even triggering autoimmunity or an immune reaction against the antibodies themselves - though the host muscle is producing the proteins so this isn't likely, it should still be examined)
• Which HIV strains will it cover? And will it be effective with co-infection?
• What is the long-term affect on the muscle?How specific is the gene insertion?

The researchers seem aware that this isn't a sure thing...yet. But it's a promising step forward in a battle against a disease that seems to be never-ending.

Australia declared measles-free

The past few years, the rate of measles infections in Australia have been less than 1 case per 1 million people. Writing in the Bulletin of the World Health Organization, immunologists at the University of Sydney have cited this criteria for declaring Australia free of measles. They expect the status to hold to 2012, with the best case estimate of 20 years (i.e. 2029). The few cases of measles occurring since 2005 have been due to foreign travelers. Measles kills approximately a million people worldwide each year, affecting mainly children under the age of 10. The virus can cause miscarriages in pregnant women and deadly encephalitis in one-tenth of those infected. Currently, the United States has been suffering outbreaks (April and August 2008) due to a decrease in vaccine coverage among school-aged children - 20% of measles patients in the United States are hospitalized because of the illness, 3 of every 1000 measles patients die. 90% of unimmunized individuals who are exposed to measles contract the respiratory disease. Measles is prevented by the MMR (measles - mumps - rubella) vaccine given to young children between 12 and 15 months of age, with a follow-up dose 4 weeks later or before beginning school. Parents have been concerned over misinformation (The original study by Wakefield that began the investigation has been found to be fraudulent with fabricated data) regarding the use of the preservative thimerosal, a mercury-based chemical, in the MMR vaccine. Scientific evidence supported by legal decisions have shown that there is no connection between the vaccine and autism, a developmental disorder diagnosed around the age of 2, the same age when the vaccine is given.

Guidelines for Vaccinating Allergic Children

The September issue of Pediatrics offers step-by-step guidelines for physicians to identify children who may have allergic reactions to vaccines and then safely vaccinate them by taking certain standard precautions.

The occurrence of allergic reactions to vaccines is approximately 1-2 per every million vaccinations. A previous reaction increases the risk for another.

With recent outbreaks of whooping cough and measles it is important to vaccinate as many children as are willing and is possible.

Being able to avoid reactions, which may reduce vaccine efficiency and scare parents from other vaccines, is important to promoting pediatric health.

Public vs Individual Health

The difference between public and individual health that often stands in the way of disease eradication and incidence decrease is simple: public health aims to do what is best for the greater good, the population as a whole; individuals aim to do what is best for them and their survival.

These two things often do not coincide. Some vaccination programs, such as smallpox, can lead to a large number of illnesses or death, but eradicates the disease in the long-run. This is good for the population, but not for the individuals who face the risk of side effects when getting the injection. There are efforts to eradicate yellow fever and polio in Africa, but villagers will not take the vaccine for fear of what it might do to their children. This is a prime example of individual health decisions not coinciding with public health goals. The increase in Measles and the reappearance of Whooping Cough in the United States has also occurred because individual health decisions to not vaccinate children do no coincide with the public health effort to keep the diseases at bay. In this scenario, no one is wrong. We each do what we believe to be best for us and ours, and the public health system continues to do what it believes is best for the population.

So how do we solve this problem?
Individuals need to keep in mind the potential effect their decision has on the public health structure and be sure they are bypassing the recommendations to avoid serious consequences only. I won't go into my recommendations of what to avoid here, but the major childhood vaccines should be sought out for healthy children, any worried parents can ask to be sure a doctor is available if side effects occur - DPT (diphtheria, pertussis/whooping cough, tetanus), MMR (measles mumps rubella), and polio. There are no longer mercury-based preservatives in pediatric vaccines. The only one containing a preservative, though it is prior to purification and so considered preservative-free at the end, is the influenza vaccine. So any questions about serious side effects have been addressed. Again, this is an individual decision and information regarding side effects is available from your pediatrician. Ask questions that pertain specifically to your child's health if you are worried. Ask them how often they see severe side effects, that will give you an indication of the actual occurrence and not just statistics printed on paper. (Vaccines are just one example of what is covered by the health system.)

The public health system needs to keep in mind that they are the amalgamation of millions of individual health decisions and structure their guidelines to be, and recommend treatments that are, beneficial to the individual if they follow them. Yes, their goal is for the health of the population, but the population is made up of individuals, if their health increases their collective health increases. Noone wants medicine that has a 20% chance of killing them just because it will ensure 40% of the population is healthy in 20 years (just a made up example).

It is time that the public health and the individual health once again join hands to solve the current health problems, before it's too late.

Cancer Vaccine From Tobacco?

Early stage testing of a vaccine for non-Hodgkins Lymphoma, a B cell proliferative disorder (cancer), that uses the tobacco plant to produce the vaccine has had promising results. The Scientist covered the story. It may be difficult to determine who to give the vaccine to, as not everyone should receive it, but those with a genetic susceptibility and at high risk for the disease will have more options.

A new HIV vaccine trial?

Despite the disappointing ending to Merck's recent HIV vaccine trial, the Partnership for AIDS Vaccine Evaluation (PAVE) is set to start a trial on the next potential vaccine - the PAVE 100 HIV vaccine trial.

The strain is a similar recombinant strain as used in the Merck vaccine, but the criteria for participants is slightly altered, which may aid in determining the effectiveness of the vaccine, but in my opinion, reduce it's generalizability. We'll see.

The AIDS Vaccine Research subcommittee voted 23-3 in favor of beginning the study. The groups responsible for the research are still reviewing the committee's recommendation to determine if they will proceed.