Saturday, March 31, 2012

Diphtheria

Holly has been feeling our baby move for a couple of weeks. This morning, she put my hand on her belly and I felt it moving for the first time.

We're experiencing and unusually high number of cases of pertussis in Washington State. This week I sent an Email to my parents and siblings asking them to get a Tdap if they haven't already had one.

I'm finishing up my discussion of tetanus, diphtheria, and acellular pertussis vaccine (Tdap) with this post on the D in Tdap and DTaP: diphtheria.


1874: Maria and Sven Larson
lost five children to diphtheria
Jone Johnson Lewis
Before the introduction of diphtheria toxoid vaccines in the mid-1940s, major diphtheria epidemics occurred roughly every 25 years. One epidemic in New England killed about a third of all children. Between 1921 and 1924, diphtheria was the leading cause of death of Canadian children 2 to 14 years of age. When immunization levels dropped, a diphtheria epidemic occurred in the former Soviet Union between 1990 and 1996. The last outbreak of diphtheria in the United States occurred in alcoholics in Seattle from 1972 to 1982.

The name diphtheria comes from the Greek word for "leather." The reason is that a tough, leather-like pseudomembrane forms over the tonsils, uvula, throat (pharynx), voice box (larynx), and sometimes into the wind pipe (trachea) of persons with respiratory diphtheria. The pseudomembrane contains dead epithelial cells, red and white blood cells, fibrin, and bacteria.

Like tetanus vaccine, diphtheria vaccine is a toxoid which stimulates the immune system to make antibodies to a toxin produced by the bacteria. Corynebacterium diphtheriae only produces diphtheria toxin when it is infected with a bacteriophage; a virus that infects bacteria. The phage carries the gene that codes for diphtheria toxin. C. diphtheriae that lack this gene are called nontoxigenic.

Although diphtheria toxin can affect any tissue in the body, its worst effects are on the heart, peripheral nerves, and kidneys. Diphtheria toxin also causes the neck to swell (edema) causing a "bullneck" appearance. Death from diphtheria can occur from suffocation either by the swelling in the neck or by a portion of dislodged pseudomembrane occluding the airway. Death can also result from a cardiac arrhythmia caused by diphtheria toxin. Because of its neurotoxicity, diphtheria toxin causes muscle weakness and paralysis, including the muscles involved in swallowing and protect the airway.

Diphtheria is usually transmitted by respiratory droplets. C. diphtheriae is not known to infect animals. Diphtheria can infect the skin, causing sores that are covered by a membrane and do not heal. Cutaneous diphtheria usually does not cause severe disease but may be a reservoir for respiratory diphtheria infections.

Diphtheria infection does not reliably result in immunity to the disease. The level of protective antibodies from immunization or infection decreases over time, which is why diphtheria toxoid is given to adults in combination with tetanus toxoid every ten years – "tetanus boosters" are actually tetanus and diphtheria boosters.

According to the Centers for Disease Control and Prevention (2010), 64% of adults 19 to 49 years of age have received a tetanus and diphtheria vaccine in the last ten years. Immunization rates decrease with age and are highest among whites, lowest among Asians. Despite the ACIP recommendation, only 8.2% of adults 19 to 64 years of age reported receiving a Tdap.

Even though there have been no cases reported in the U.S. since 2003, there is a risk of importation from countries where diphtheria remains endemic. Tetanus spores are present in the environment, and the incidence of pertussis has been increasing in recent years. These three diseases are still a risk to people living in the U.S., but they are controllable with immunization.

Additional information:

ማቴዎስ ጳውሎስ

References

Centers for Disease Control and Prevention. (2010). Adult vaccination coverage – United States, 2010. Morbidity and Mortality Weekly Report, 61(4), 66-72. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a2.htm.

Centers for Disease Control and Prevention. (2011). Diphtheria. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/diptheria_t.htm.

Golaz, A., Hardy, I. R., Strebel, P., Bisgard, K. M., Vitek, C., Popovic, T., & Wharton, M. (2000). Epidemic diphtheria in the Newly Independent States of the former Soviet Union: implications for diphtheria control in the United States. Journal of Infectious Diseases, 181(Supple. 1), S237-S243. http://jid.oxfordjournals.org/content/181/Supplement_1/S237.long.

Harnisch, J. P., Tronca, E., Nolan, C. M., Turck, M., & Holmes, K. K. (1989). Diphtheria among alcoholic urban adults. A decade of experience in Seattle. Annals of Internal Medicine, 111(1), 71-82.

MacGregor, R. R. (2009). Corynebacterium diphtheriae. In G. L. Mandell, J. E. Bennett, & R. Dolin (Eds.), Mandell, Douglas, and Bennett's principles and practice of infectious diseases (7th ed.). [Electronic version].

Overturf, G. D. (2009). Corynebacterium diphtheriae. In S. S. Long (Ed.) Principles and practice of pediatric infectious diseases (3rd Ed.). [Electronic version].

Vitek, C. R. & Wharton, M. (1998). Diphtheria in the former Soviet Union: reemergence of a pandemic disease. Emerging Infectious Diseases, 4(4), 539-550. http://wwwnc.cdc.gov/eid/article/4/4/98-0404_article.htm.

Vitek, C. R. & Wharton, M. (2008). Diphtheria toxoid. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines (5th Ed.). [Electronic version].

Saturday, March 24, 2012

The safety of Tdap in pregnancy

The prettiest 20-weeks pregnant
woman I've ever seen!
Holly stopped at a produce stand yesterday to stock up on fruits and vegetables. We're both making an extra effort to eat healthier and take care of ourselves. We're responsible for another person other than ourselves and each other. Of course, we're much more careful about what Holly eats and what she's exposed to.

People are justifiably concerned about the safety of vaccines during pregnancy. In response to my post on tetanus, I received a request to provide studies on the safety of tetanus, diphtheria, and acellular pertussis vaccines (Tdap) during pregnancy.

The data and studies that support the Advisory Committee on Immunization Practice (ACIP) recommendations are found in the recommendations themselves. These are published in the CDC's Morbidity and Mortality Weekly Report (MMWR).
Be forewarned: they're not easy to read.

As I wrote in my response to anonymous, the ACIP recommendations for use of Tdap in pregnant women cited two studies (Gall et al., 2011 and Talbot et al., 2010) that "did not suggest any elevated frequency or unusual patterns of adverse events in pregnant women who received Tdap"

The ACIP examined the safety of Tdap in pregnancy in detail in a previous recommendation.

The safety of tetanus toxoid vaccines in pregnancy was first evaluated in the 1960's and the safety of diphtheria vaccine in pregnancy was evaluated in the 1970's. Since the mid 1970's, the World Health Organization (WHO) Expanded Programme on Immunizations (EPI) has included a recommendation for the use of tetanus toxoid in pregnant women to prevent neonatal tetanus. Since the early 1980's, the CDC and American College of Obstetricians and Gynecologists have recommended tetanus and diphtheria vaccine (Td) for under-immunized pregnant women.

Both tetanus toxoid and diphtheria toxoid vaccines, together and separately, have over 30 years of safe use during pregnancy.

There were several studies of whole cell pertussis vaccines in pregnancy in the 1930's and 1940's. No serious adverse reactions in either mother or baby were recorded. Remember that whole-cell pertussis vaccines have around 3,000 antigens compared to the Tdap vaccines currently licensed in the U.S. which contain only three or five inactivated pertussis toxins.

In their General recommendations on immunization, the ACIP states, "Risk to a developing fetus from vaccination of the mother during pregnancy is theoretical. No evidence exists of risk to the fetus from vaccinating pregnant women with inactivated virus or bacterial vaccines or toxoids." The American College of Obstetricians and Gynecologists echoes that statement in their Update of immunization and pregnancy: Tdap.

ACOG also states, "Ideally, vaccines should be administered before conception." For reasons other than concern about the safety of the vaccine during pregnancy, Holly received her Tdap in 2008.

Additional information:
References

American College of Obstetricians and Gynecologists. (2012). Update on immunization and pregnancy: tetanus, diphtheria, and pertussis vaccination. Obstetrics and Gynecology, 119(3), 690-691. http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Update_on_Immunization_and_Pregnancy_Tetanus_Diphtheria_and_Pertussis_Vaccination.

Centers for Disease Control and Prevention. (1983). Recommendations of the Immunization Practices Advisory Committee general recommendations on immunizations. Morbidity and Mortality Weekly Report, 32(1), 13-17. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001226.htm.

Centers for Disease Control and Prevention. (2008). Prevention of pertussis tetanus, and diphtheria among pregnant and postpartum women and their infants. Morbidity and Mortality Weekly Report, 57(4), 1-47, 51. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5704a1.htm.

Centers for Disease Control and Prevention (2011). General recommendations on immunizations. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 60(2), 1-60. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm.

Centers for Disease Control and Prevention. (2011). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged <12 months – Advisory Committee on Immunization Practices (ACIP), 2011. Morbidity and Mortality Weekly Report, 60(41), 1424-1426. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6041a4.htm.

Edwards, K. M. & Decker, M. D. (2008) Pertussis vaccines. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines (5th Ed.). [Electronic version].

Gall, S. A., Myers, J., & Pichichero, M. (2011). Maternal immunization with tetanus-diphtheria-pertussis vaccine: effect on maternal and neonatal serum antibody levels. American Journal of Obstetrics & Gynecology, 204(4), 334.e1-5. doi.org/10.1016/j.ajog.2010.11.024.

Offit, P. A., Quarles, J., Gerber, M. A., Hackett, C. J., Marcuse, E. K., Kollman, T. R. et al. (2002). Addressing parents’ concerns: do multiple vaccines overwhelm or weaken the infants immune system? Pediatrics, 109(1), 124-129. http://pediatrics.aappublications.org/content/109/1/124.full.

Talbot, E. A., Brown, K. H., Kirkland, K. B., Baughman, A. L., Halperin, S. A., & Broder, K. R. (2010). The safety of immunizing with tetanus-diphtheria-acellular pertussis vaccine (Tdap) less than 2 years following a previous tetanus vaccination: experience during a mass vaccination campaign of healthcare personnel during a respiratory illness outbreak. Vaccine, 28(50), 8001-8007. doi:10.1016/j.vaccine.2010.09.034.

Wassilak, S. G. F., Roper, M. H., Kretsinger, K., Orenstein, W. A. (2008). Tetanus toxoid. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds) Vaccines (5th Ed.). [Electronic version].


 


 

Sunday, March 18, 2012

Tetanus (lockjaw)

School in Muti, Ethiopia
One of the more enjoyable outreaches that I did while working in Ethiopia was going out to schools to vaccinate school-aged girls and young women (we vaccinated the boys too but, according to the Ethiopian Ministry of Health immunization schedule, we weren't supposed to). We would hike to villages where at least some of the children had never seen a faranji. Watching their reaction to me was fun. First they'd be a little frightened, and then they'd get curious - they'd sneak up behind me, quickly touch my skin or my hair, and then run away. Once the children had warmed up to me, I'd spend a little time playing with them before we had to hike back to the health center.

Aside from protecting the vaccine recipient, one of the goals of vaccinating woman and girls who will soon be of child-bearing age against tetanus is to protect their babies from neonatal (newborn) tetanus.

Tetanus is the only vaccine-preventable disease that is not transmitted from person to person or, in the case of rabies and yellow fever (both of which I am immunized against), from animal to person. In my opinion, tetanus is one of the most frightening vaccine-preventable diseases and, to top it off, humans do not develop immunity to tetanus after being infected with the bacteria.

Tetanus is caused by a toxin produced by a bacteria, Clostridium tetani. Tetanospasmin, or tetanus toxin, is the second most poisonous substance known (the most poisonous substance is produced by a bacteria of the same genus, C. botulinum. That's right - Botox). C. tetani is found primarily in soil but is also found in the gastrointestinal tract of animal and humans.

C. tetani produces spores that are resistant to conditions that normally kill bacteria – even boiling will not kill C. tetani spores. Tetanus spores are introduced into tissue usually through wounds or, in the case of neonatal tetanus, through the umbilical stump. Tetanus has also been associated with piercings, injection drug use, chronic otitis media (ear infection), animal bites, burns, and, on rare occasions, no source of infection is identified.

Risus sardonicus
CDC/ AFIP/C. Farmer
Tetanus toxin is released from the bacteria and enters motor nerves and blood. The toxin is transported to the spinal cord and brain where it blocks the action of inhibitory neurotransmitters. Reflexive responses are unopposed, resulting in painful muscle contractions. With localized tetanus, the spasms are limited to the part of the body infected with the tetanus bacteria. In generalized tetanus, every muscle group in the body contracts. Ironically, spasms of facial muscle make the person appear as if she or he is smiling. This is called risus sardonicus. A person with tetanus has no reason to smile; the muscle spasms are excruciatingly painful and consciousness is not lost, so the person remains completely aware.

People with generalized tetanus or cephalic (head) tetanus usually require critical care with endotracheal intubation and mechanical ventilation. They frequently require sedation and sometimes drug-induced paralysis to manage the spasms. People who recover from severe tetanus often have psychiatric problems as the result of their ordeal.

Tetanus vaccine is inactivated tetanus toxin, also known as tetanus toxoid. In response to the vaccine, the immune system makes antibodies to tetanus toxin. These antibodies do not kill C. tetani or prevent infection, but prevent tetanus toxin from entering the nervous system and causing tetanus. A person infected with C. tetani will need to be treated with antibiotics to kill the bacteria.

Neonatal tetanus
CDC
Antibodies to tetanus toxin pass through the placenta to the fetus, providing the newborn baby protection against neonatal tetanus. Babies receive their primary diphtheria, tetanus, and acellular pertussis (DTaP) series at 2, 4, and 6 months of age. Until then, they are protected by their mother's antibodies.

Adults who have received a primary diphtheria, tetanus, and pertussis series (DTP or DTaP) should receive tetanus and diphtheria (Td) boosters every ten years. Pregnant women who have completed a primary DTP/DTaP series should receive one dose of tetanus, diphtheria, and acellular pertussis vaccine (Tdap) either before becoming pregnant or after 20 weeks of gestation. Pregnant women who have not completed a tetanus primary series should receive three doses of tetanus and diphtheria vaccine (Td) including one dose of Tdap.

Additional information

References

American College of Obstetrics and Gynecologists. (2012). Update on immunization and pregnancy: tetanus, diphtheria, and pertussis vaccination. ACOG committee opinion No. 521. Obstetrics and Gynecology, 119(3), 690-691. http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Update_on_Immunization_and_Pregnancy_Tetanus_Diphtheria_and_Pertussis_Vaccination.

Arnon, S. S. (2011). Tetanus (Clostridium tetani). In R. M. Kliegman, B. F. Stanton, J. W. St. Geme III, N. F. Schor, & R. E. Behrman (Eds.). Nelson textbook of pediatrics (19th Ed.). [Electronic version].

Centers for Disease Control and Prevention. (2011). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged <12 months – Advisory Committee on Immunization Practices (ACIP), 2011. Morbidity and Mortality Weekly Report, 60(41), 1424-1426. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6041a4.htm.

Reddy, P. & Bleck, T. P. (2010). Clostridium tetani (tetanus). In G. L. Mandell, J. E. Bennett, & R. Dolin (Eds). Mandell, Douglas, and Bennett's principles and practice of infectious diseases (7th ed.). [Electronic version].

Wassilak, S. G. F., Roper, M. H., Kretsinger, K., Orenstein, W. A. (2008). Tetanus toxoid. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds) Vaccines (5th Ed.). [Electronic version].


Monday, March 12, 2012

Pertussis vaccines

Our baby at 19 weeks
I took the day off and went with Holly to see the midwife. Everything looks good! Holly had hoped to know the sex of our baby with today's ultrasound, but the US tech wasn't able to get a good enough picture to tell. We're happy just knowing that our baby looks healthy.

I've spent the last two weeks reading up on pertussis vaccines to prepare for writing this post. I have decided to address adult pertussis immunization and infant pertussis immunization separately.

I almost feel like I should use a "good news-bad news" format for this post. Pertussis vaccines are highly effective but, because immunity to pertussis from either natural infection or vaccination wanes, it is difficult to control the disease.

Prior to the development of pertussis vaccines, there were 115,000 to 270,000 cases of pertussis and 5,000 to 10,000 deaths from pertussis in the U.S. every year. The use of pertussis vaccine in the U.S. has resulted in a 99% reduction in the number of cases of pertussis.
CDC, 2002
Pertussis vaccines are highly effective but, because immunity to pertussis from either natural infection or vaccination only lasts about 10 years, the incidence of pertussis in the U.S. has increased over the last 30 years. California recently had a large pertussis epidemic and, here in Washington State, there is currently an outbreak in Snohomish County.

All pertussis vaccines licensed in the U.S. are combination vaccines with tetanus and diphtheria toxoids (inactivated toxins from the bacteria that cause those diseases). There are two types of pertussis-containing vaccines licensed in the U.S.:

Whole cell pertussis vaccines
Whole cell pertussis vaccines (DTP or DTwP), which are no longer used in the U.S., contained killed Bordetella pertussis bacteria. These vaccines include around 3,000 antigens. These vaccines are highly effective and are still used in some countries, but the high number of antigens in whole cell vaccines increased the risk of side effects.

Acellular pertussis vaccines
Bordetella pertussis produces toxins that allow it to attach to and kill cells in the respiratory tract. Acellular ("without cells") pertussis vaccines contain inactivated pertussis toxins instead of the whole organism. Because these vaccines contain 2 to 5 pertussis antigens, side effects occur much less frequently than with the old whole cell pertussis vaccines.

Cocooning
In the U.S., the majority of cases of pertussis are in babies too young to have received three doses of DTaP (Babies receive DTaP at 2, 4, and 6 months of age. Until then, they are susceptible to pertussis). Over half of these babies get pertussis from one of their parents, most often, from their mother.

To prevent babies from getting pertussis, the American College of Obstetricians and Gynecologists (ACOG) and the CDC's Advisory Committee on Immunization Practices (ACIP) recommend a dose of Tdap after 20 weeks of gestation (late 2nd trimester or in the 3rd trimester) for pregnant women who have not previously received a dose of Tdap. This includes women who received DTP or DTaP during childhood.

Both the ACOG and ACIP also recommend a dose of Tdap for everyone who has or anticipates having contact with a baby less than 1 year of age. This includes brothers and sisters, grandparents, and, most importantly, fathers (As a health care provider, I received my Tdap in 2006; before it was recommended for the general population). This strategy is known as "cocooning."

Additional protection
Pertussis antibodies are actively transported across the placenta to the baby in the womb. In fact, the concentration of pertussis antibodies is higher in cord blood than it is in the mother's blood. So, in addition to preventing transmission of pertussis from mother to baby, giving a Tdap to a pregnant woman may also provide the baby with passive immunity to pertussis in its first months of life.

Additional information:

References:

American College of Obstetricians and Gynecologists. (2012). Update on immunization and pregnancy: tetanus, diphtheria, and pertussis vaccination. Obstetrics and Gynecology, 119(3), 690-691. http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Update_on_Immunization_and_Pregnancy_Tetanus_Diphtheria_and_Pertussis_Vaccination.

Centers for Disease Control and Prevention. (2002). Pertussis – United States, 1997-2000. Morbidity and Mortality Weekly Report, 51(4), 73-76. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5104a1.htm.

Centers for Disease Control and Prevention. (2011). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. Morbidity and Mortality Weekly Report, 60(1), 13-15. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6001a4.htm.

Centers for Disease Control and Prevention. (2011). Updated recommendations for use of tetanus toxoid, reduced diphtheria and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant <12 months – Advisory Committee on Immunization Practices (ACIP), 2011. Morbidity and Mortality Weekly Report, 60(41), 1424-1426. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6041a4.htm.

Edwards, K. M. & Decker, M. D. (2008) Pertussis vaccines. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines (5th Ed.). [Electronic version].

Gall, S. A. (2008). Vaccines for pertussis and influenza: recommendations for use in pregnancy. Clinical Obstetrics and Gynecology, 51(3), 486-497. doi:10.1097/GRF.0b013e318181dde1.

Gall, S. A., Myers, J., & Pichichero, M. (2011). Maternal immunization with tetanus-diphtheria-pertussis vaccine: effect on maternal and neonatal serum antibody levels. American Journal of Obstetrics & Gynecology, 204(4), 334.e1-5. doi.org/10.1016/j.ajog.2010.11.024.

Lavin, J., Broutin, H., Harville, E. T., & Bjørnstad, O. N. (2011). Imperfect vaccine-induced immunity and whooping cough transmission to infants. Vaccine, 29(1), 11-16. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997163.

Offit, P. A., Quarles, J., Gerber, M. A., Hackett, C. J., Marcuse, E. K., Kollman, T. R. et al. (2002). Addressing parents' concerns: do multiple vaccines overwhelm or weaken the infant's immune system? Pediatrics, 109(1), 124-129. http://pediatrics.aappublications.org/content/109/1/124.full.

Quinello, C., Quintilio, W., Carneiro-Sampaio, M., & Palmeira, P. (2010). Passive acquisition of protective antibodies reactive with Bordetella pertussis in newborns via placental transfer and breast-feeding. Clinical Immunology, 72(1), 66-73. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3083.2010.02410.x/full.

Wendelboe, A. M., Van Rie, A., Salmaso, S., & Englund, J. A. (2005). Duration of immunity against pertussis after natural infection or vaccination. Pediatric Infectious Disease Journal, 24(5), S58-S61. http://journals.lww.com/pidj/Fulltext/2005/05001/Duration_of_Immunity_Against_Pertussis_After.11.aspx.