Vaccines less effective in kids exposed to PCBs.

Aug 06, 2010

Heilmann, C, E Budtz-Joergensen, F Nielsen, B Heinzow, P Weihe and P Grandjean. 2010. Serum concentrations of antibodies against vaccine toxoids in children exposed perinatally to immunotoxicants. Environmental Health Perspectives http://dx.doi.org/10.1289/ehp.1001975.




flickr/Brittany Randolph
 
Children exposed to PCBs in their first years of life are less likely to develop immunity to disease after they are vaccinated, according to a new study. Overall, the study shows that cumulative exposure to environmental PCBs – particularly leading up to 18 months of age – may decrease immune system development, leaving vaccinated children still at risk for developing disease.
 
 
 
 
 

Context

Polychlorinated biphenyls (PCBs) are environmental contaminants that were commercially produced for a range of applications since the 1920s. PCBs are now banned worldwide, although they bioaccumulate and persist in the environment and food.

The chemicals are found in measurable amounts in most people, as they build up in human bodies over time. Babies are exposed to PCBs during fetal development, while nursing or drinking formula and thereafter from diet.

PCBs – like dioxins, can affect the ability of the human immune system to fight disease.  PCBs are also associated with cancer and effects on reproductive, nervous, and endocrine systems.  For instance, PCB exposure is associated with reduced intelligence in people, due to effects on thyroid function and brain size.

Vaccines stimulate the immune system to make antibodies and related immune cells that are specific for a given microbe. The antibodies attach to proteins on the microbe and mark it for destruction by other immune cells. Thus, the more antibodies floating around in a person’s blood, the faster their response to microbial invasion.

The increase in microbe-specific antibodies and immune cells caused by vaccination results in “immunological memory.” It is this “memory” that confers immunity. Essentially, after being vaccinated, a person’s immune system is primed and can respond very quickly if he or she is exposed to the disease-causing microbe again. A quick response means a quick recovery, often before the person even feels sick.

The human immune system develops over time – beginning before birth – and continuously adapts to new microbes as they are encountered, either through vaccination or by getting the disease, as with flu. If a person’s immune system is compromised due to exposure to an environmental contaminant, like dioxin or PCBs, not make enough antibodies and other immune cells to effectively fight a given disease. This is a significant concern, particularly with life threatening diseases.

Two such diseases are tetanus and diphtheria. Children in the United States are first vaccinated for these illnesses before thier first birthdays. Tetanus – also called “locked jaw” – is a serious, often fatal condition caused by a bacterium that infects a cut or deep puncture wound. Patients with tetanus experience excessive muscle contraction, stiffness, altered heart rate and nerve cell damage. Diphtheria is a contagious, potentially fatal, upper respiratory tract disease.  Both diseases are rare in the United States and other populations with high rates of vaccination.

What did they do?

Researchers measured PCB concentrations and antibodies in the blood of pregnant women and their children from the Faroe Islands.  The Faroe Islands are a Nordic fishing community in the North Atlantic Ocean, near Iceland.  PCB exposure among the Faroese can be quite high, due to PCB contamination of pilot whale blubber, which is eaten by many, but not all Faroese.

The researchers determined cumulative PCB exposures and then compared the PCB levels to antibody concentrations produced against diphtheria and tetanus in children vaccinated for these diseases to determine if the chemicals would reduce antibody production and affect the children's ability to fight disease. The “ability to fight disease” was based on post-vaccination blood antibody levels.

Blood samples were taken from the mothers in the 32nd week of pregnancy and from their children at 3, 5, 12 and 18 months and at 5 and 7 years of age. Breastmilk was collected from the mothers on the fourth or fifth day after birth. The number of children participating in the study varied from a few hundred to several hundred at each age point.

Blood and milk samples were analyzed for total PCB contamination. Antibody concentrations against tetanus and diphtheria were measured in all blood samples. Children received vaccinations against tetanus and diphtheria, following a standard vaccination schedule, at 3, 5, and 12 months, and then again at 5 years.

The researchers used statistical analysis to determine if blood PCB levels predicted the concentrations of antibodies against diphtheria and tetanus in the children at different ages. In their analysis, researchers considered the effects of age, sex, birth weight, maternal smoking during pregnancy, duration of breast-feeding, and mercury exposure on the relationship between PCB exposure and antibody concentrations.

What did they find?

The researchers found that increased blood PCBs were strongly associated with decreased antibody concentrations in the 5-year-old children during the three weeks after receiving their booster vaccines for diphtheria. Moreover, before receiving the booster vaccine, 37 percent of the 5-year-olds had antibody concentrations that were insufficient for protection. This insufficiency was associated with higher PCB levels in maternal milk and blood taken at 18 months and 5 years of age.

The blood PCB levels measured at 18 months appear to be particularly relevant to immune system function. For instance, at 18 months, diphtheria antibodies were reduced among children with high PCB loads. In addition, for every doubling of PCB concentrations in maternal milk and 18-month blood serum, the 5-year olds were 30 percent less likely to have enough anti-diphtheria antibodies to provide protection. At age 7, children with high PCBs at 18 months had reduced concentrations of antibodies against both tetanus and diphtheria.

In addition to these main findings, the researchers made some other interesting observations. For example, healthy children vary considerably in their innate ability to respond to vaccines. This is likely due to other environmental and genetic factors, in addition to PCB loads.

Furthermore, toward the end of the study, some children were vaccinated with newer vaccine formulations that included pertussis and polio antigens, in addition to diphtheria and tetanus. These newer, multi-microbe vaccines resulted in lower antibody concentrations for tetanus and diphtheria, compared to earlier vaccines that did not include pertussis or polio. Vaccines are known to interfere with each other. These data suggest that vaccines given one at a time, rather than as a set, may be more effective over the long-term.

What does it mean?

Cumulative PCB exposure during development and early childhood – particularly levels measured around 18 months – can reduce the development of antibodies in response to diphtheria and tetanus vaccines.

This reduction can potentially increase the risk that vaccinated children are still vulnerable to contracting the diseases. A minimum antibody concentration is required for a quick immune response when a person is exposed to a disease. Immunity is compromised if a person’s blood antibody concentrations are low.

The authors speculate that 18 months is a critical window for immune development and that high PCB body burdens at 18 months may be particularly harmful to immune function during childhood.

The effectiveness of vaccinations is an important public health question, because vaccinations protect large numbers of people from serious diseases, including polio and small pox. If environmental contaminants, such as PCBs, reduce the effectiveness of vaccines by decreasing immune responses to vaccines, then individuals may no longer be adequately protected. Reduced protection on a large scale would make disease outbreaks more likely.

One strength of this study is that the researchers were able to follow a group of children from birth through age 7, with data collected at several time points in between. However, not all children were available at all time points. This resulted notably in a lower sample size at 18 months, which was unfortunate given the apparent importance of PCB loads at that age.

The study could have been strengthened by an examination of memory B cells (those cells that are ready to make antibody at a moment's notice) in the children, as opposed to simply circulating antibodies.

Researchers also measured mercury concentrations in cord blood, maternal hair at birth and the children’s hair during the study period up to 7 years of age. They did not detect a predictable effect of mercury on antibody concentrations.

Resources

Diphtheria vaccination. Department of Health and Human Services. Centers for Disease Control and Prevention.

Polychlorinated biphenyls (PCBs). U.S Environmental Protection Agency.

Tetanus (lockjaw) vaccination. Department of Health and Human Services. Centers for Disease Control and Prevention.

 

 

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