Disease eradication

First, Holly had another ultrasound on last week – it's a boy! (but I'm not going to show you that picture).

Next, Mary had surgery three weeks ago. The neurosurgeon removed about 90 to 95 percent of the tumor. Mary transferred out of the hospital into a skilled nursing facility yesterday. She is enthusiastically participating in her therapies and has regained some strength in her left side. Thanks for your prayers.

I forgot to mention that I became a published author May 1^st: Improving Immunization Coverage in a Rural School District in Pierce County, Washington. I wrote the article but, since I wasn't directly involved in the study, I'm the last author listed. Now I need to get my cerebral malaria paper published!

Disease eradication

As I discussed in my post on diseases that have been eliminated from the U.S. by vaccines, the difference between disease elimination and eradication is that elimination is the reduction of the incidence of a disease to zero within a geographic region and elimination is the global incidence of a disease to zero. Another important distinction is that once a disease has been eradicated, further efforts to control that disease are no longer necessary.

So far, smallpox is the only disease that has been eradicated, so smallpox vaccination is no longer recommended for the general population. I'm a baby boomer with a smallpox vaccination scar. Holly is Generation X and does not have a smallpox vaccination scar.

There are currently two ongoing disease eradication initiatives: poliomyelitis ("polio") and dracunculiasis (Guinea worm disease).

For a disease to be considered eradicable it must meet a number of biological, economic, political, and societal criteria. Walter Dowdle outlined three primary indicators:

• There must be an effective intervention to interrupt transmission
• There must be a diagnostic tool that is sensitive and specific enough to detect the infection
• Humans must be essential to the lifecycle of the infecting agent

For most eradicable diseases, a vaccine is the intervention used to interrupt transmission, but that's not the case for dracunculiasis.

For smallpox, the diagnostic tool used to detect infection was clinical presentation: a person infected with the variola (smallpox) virus had the characteristic lesions of that disease. Unlike some other infections, there was no asymptomatic carriage of variola virus. People who were infected got the disease. For polio, the diagnostic tool is clinical presentation and detection of poliovirus in stool.

In general, for humans to be essential to the lifecycle of the infecting agent means that there can be no non-human reservoirs. Two examples of diseases for which there are non-human reservoirs that come to mind are yellow fever, which infects humans and monkeys, and influenza, which infects other mammals and birds.

I won't go into the details of the economic/political/societal requirements for disease eradication. The short version is that there must be sustained political will to eradicate a disease. Since disease eradication is a global effort, you can imagine the complexities of arriving at an agreement that eradication of a disease is a worthwhile goal.

Removing a Guinea worm
CDC/ The Carter Center

The strategies used to eradicate a disease will vary with the disease and its mode of transmission. There is no vaccine for Guinea worm disease, which is transmitted through water. Instead, filtering or boiling drinking water are two of the techniques used to prevent transmission.

Polio eradication relies on three vaccination strategies:

• High routine coverage with oral polio vaccine
• National Immunization Days
• Supplemental "mop-up" campaigns

As the immunization outreach coordinator at the Chiri Health Center in Ethiopia, I was involved with achieving and maintaining high routine immunization coverage in the neighboring villages. During National Immunization Days, our clinic staff would be recruited to go door-to-door to administer oral polio vaccine to all of the infants and young children within those households. I recall spending part of a day walking around Addis Ababa looking for chalk for the vaccinators to mark the doors of houses they had visited. Fortunately, there were no outbreaks of polio in our area that required mop-up immunization.

In addition to immunization, the clinic staff were responsible to report any new cases of acute flaccid paralysis (AFP) that might have been paralytic polio. Surveillance is an integral part of an eradication program. Had we seen a case of AFP in the clinic, we would have been required to send a stool specimen from the child to Addis Ababa to test for the presence of poliovirus.

Transmission of one of the three wild poliovirus types has not been detected anywhere in the world since 1999. Wild poliovirus transmission has been interrupted in all but four countries: Afghanistan, India, Nigeria, and Pakistan. Poliovirus transmission had ceased, but has been reestablished in Angola, Chad, and the Democratic Republic of the Congo. Outbreaks of polio occur in countries where poliovirus has been reimported.

Until polio has been eradicated, there is a continuing threat of importation from countries where poliovirus continues to be transmitted.

I'll spend more time talking about polio and polio vaccines in a few months when our baby is due for his first dose of polio vaccine.

More information:

• Global Polio Eradication Initiative
• The Carter Center: Guinea Worm Disease Eradication

References:

Dowdle, W. A. (1998). The principles of disease elimination and eradication. Morbidity and Mortality Weekly Report, 48(Supple. 1), 23-27. http://www.cdc.gov/mmwr/preview/mmwrhtml/su48a7.htm.

Fine, P. E. M. & Mulholland, K. (2008). Community immunity. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines (5th Ed.) [Electronic version].

Hadler, S. C., Dietz, V., Okwo-Bele, J. M., & Cutts, F. T. (2008). Immunization in developing countries. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines (5th Ed.) [Electronic version].

Heymann, D. L. (2011). Disease eradication and control. In R. L. Guerrant, Walker, D. H., & Weller, P. F. (Eds.) Tropical infectious diseases, principles, pathogens and practice (3^rd Ed.). [Electronic version].

Olsen, B., Munster, V. J., Wallensten, A., Waldenström, J., Osterhaus, A. D. M. E., Fouchier, R. A. M. (2006). Global patterns of influenza A virus in wild birds. Science, 21(312), 384-388. http://www.sciencemag.org/content/312/5772/384.full.

Community immunity (herd immunity)

Pardon my hiatus. I made a lateral transfer to epidemiology and I'm still getting used to my new work hours.

Craig and Mary, April 23, 2005
Father and mother of the bride



I had planned to post the following thread on Mother's Day. Instead, my father-in-law and I accompanied Mary, my mother-in-law, to an emergency department where she had a head CT and then a brain MRI which disclosed a glioblastoma – the worst type of brain tumor.

Holly and I met in 2003 while I was taking care of Seth, who had sustained a severe traumatic brain injury in a motor vehicle accident. Seth has remains in a minimally conscious state. Despite her rheumatoid arthritis, Mary has cared for Seth at home for nearly seven years. Now, Mary is in the care of some of the same nurses who cared for Seth eight and a half years ago and the best neurosurgeon I have known in my career as a neuro nurse. She will have surgery on Monday.

Mary and Craig welcomed me into their home as their son seven years ago. Mary has been an inspiration to everyone who knows her. Please be in prayer for her.

Community immunity: 

Another study on the incidence of measles was published shortly after my last post: Assessment of the 2010 global measles mortality reduction goal. The investigators found that the number of deaths from measles worldwide has decreased by 74% between 2000 and 2010. Measles outbreaks in Africa and immunization program delays in India prevented the goal of 90% reduction in measles deaths from being achieved. Forty-seven percent of the estimated 139,300 measles deaths in 2010 occurred in India and 36% occurred in Africa.

In previous posts I've talked about some ways that vaccines indirectly protect people other than the recipient. Maternal antibodies are transported across the placenta, protecting newborn babies from neonatal tetanus and may protect babies against pertussis. Cocooning is another strategy to protect babies against pertussis.

Communicable diseases are diseases that are transmitted from one person to another. For a communicable disease to be transmitted, a susceptible person must be exposed to the infecting agent. Most vaccine-preventable diseases are transmitted by contact with someone who is infected with a virus or bacterium (Yellow fever, which is transmitted by mosquitoes, is one exception that comes to mind. Tetanus is a vaccine-preventable disease that is not communicable). The probability that a susceptible person will be exposed to an infected person decreases with the proportion of immune people in a population. Therefore, susceptible individuals are protected by other people's immunity. This is known as "community immunity" or "herd immunity."

Last year there were 222 cases of measles in the U.S. Seventy-two cases were imported from outside of the U.S., and 128 cases were known to be associated with the imported case (CDC, 2012b). The basic reproductive number (R₀, or "R naught") for measles is 14, which means that in a susceptible population, a person with measles will transmit the virus to 14 other people, who will each transmit it to 14 people until there are no longer enough susceptible people in the population to sustain transmission. The size of the measles outbreaks in U.S. last year were limited by the small number of people in the country who are susceptible to measles; that is, most people in the U.S. are immune to measles. The national average for receipt of at least one dose of measles-containing vaccine (MCV) is 90% (CDC, 2012a).

Examples of indirect vaccine protection:

A recent study that demonstrated a protective effect of vaccines on people other than the recipients was the 2010 Hutterite study. During the 2008-2009 influenza season the study investigators randomized 46 Hutterite colonies in western Canada. Children ages 3 to 15 years in 22 of the colonies received seasonal influenza vaccine and children in 24 of the colonies received hepatitis A vaccine as a control (rather than a placebo). During the flu season, the numbers of cases of influenza were counted in all of the participating colonies. At the end of the flu season, the numbers of cases of influenza in the colonies in which children received influenza vaccine and colonies in which children received hepatitis A vaccine were compared. The study investigators found that the seasonal influenza vaccine given to children was 61% effective in preventing flu in colony members who did not receive the vaccine (Loeb et al., 2010).

From 1998 to 2003, 7-valent pneumococcal conjugate vaccine dramatically reduced the incidence of invasive pneumococcal disease (IPD) in children less than 5 years of age who received the vaccine. At the same time, the incidence of IPD also decreased in all age groups, with the largest rate of reduction in people aged 65 years and older. The decrease in incidence was seen only in seven pneumococcal serotypes included in the vaccine, so it is unlikely that the decreased incidence was caused by some other factor. Overall, 69% of the protective effect of pneumococcal vaccine was seen in people who had not received the vaccine (CDC, 2005).

One more example is in the near elimination of deaths due to chickenpox (yes, people die from chickenpox) after the introduction of chickenpox vaccine. The reduction in the number of deaths due to chickenpox was seen in all age groups, not just those who had received the vaccine (Marin, Zhang, & Seward, 2011).

In a previous post, I talked about diseases that have been eliminated from the U.S. by vaccines. Next, I'd like to discuss disease eradication.

More information:

• National Institute of Allergy and Infectious Diseases: Community Immunity ("Herd" Immunity)
• The College of Physicians of Philadelphia: Herd Immunity

References:

Centers for Disease Control and Prevention. (2005). Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease – United States, 1998-2003. Morbidity and Mortality Weekly Report, 54(36), 893-897. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5436a1.htm.

Centers for Disease Control and Prevention. (2012). Epidemiology and prevention of vaccine-preventable diseases (12^th Ed.). http://www.cdc.gov/vaccines/pubs/pinkbook/index.html.

Centers for Disease Control and Prevention. (2012). Measles – United States, 2011. Morbidity and Mortality Weekly Report, 61(15), 253-257. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6115a1.htm.

Fine, P. E. M. & Mulholland, K. (2008). Community immunity. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines (5th Ed.) [Electronic version]

Heyman, D. L. (2011). Disease eradication and control. In R. L. Guerrant, D. H. Walker, & P. F. Weller (Eds.). Tropical infectious diseases: principles, pathogens and practice (3^rd Ed.). [Electronic version].

Loeb, M., Russell, M. L., Moss, L., Fonesca, K., Fox, J., Earn, D. J. D. et al. (2010). Effect of influenza vaccination of children on infection rated in Hutterite communities. JAMA, 303(10), 943-950. http://jama.ama-assn.org/content/303/10/943.full.

Marin, M., Zhang, J. X., & Seward, J. F. (2011). Near elimination of varicella deaths in the US after implementation of the vaccination program. Pediatrics, 128(2), 214-220. http://pediatrics.aappublications.org/content/early/2011/07/21/peds.2010-3385.full.pdf.

National Institute of Allergy and Infectious Diseases. (2010). Community immunity ("herd" immunity). http://www.niaid.nih.gov/topics/pages/communityimmunity.aspx.

Reinberg, S. (2012). Measles deaths falling worldwide. HealthDay News. http://consumer.healthday.com/Article.asp?AID=664027.

Simons, E., Ferrari, M., Fricks, J., Wannemuehler, K., Anand, A., Burton, A. et al. (2012). Assessment of the 2010 global measles mortality reduction goal: results from a model of surveillance data. Lancet, DOI:10.1016/S0140-6736(12)60522-4. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60522-4/fulltext.

Measles

My beautiful bride
April 23, 2005

Seven years ago today I married my precious wife. From the moment I saw her I knew that she is a woman to be adored and I prayed that I would be the man who could spend his life loving her. She is the answer to my prayer and my treasure.

Happy anniversary Holly!

In my post last week I touched on measles vaccine effectiveness. I had already decided to write this week's post on measles before the Centers for Disease Control and Prevention (CDC) published its summary of measles in the United States, 2011.

Last year there were 222 cases of measles in the U.S. Ninety percent of those cases were either imported from other countries or linked to imported cases. More than half of the imported measles cases came from Europe, where there were over 30,000 cases of measles last year. The highest incidence of measles in Europe was in infants too young to receive the measles vaccine.

Eighty six percent of measles cases in the U.S. last year were in unvaccinated people or people whose vaccination status was unknown. Most of the unvaccinated cases were eligible to receive measles, mumps, and rubella vaccine (MMR), but 18 of those cases were children too young to receive MMR. Seventy people (32% of measles cases) were hospitalized with measles in the U.S. last year.

Measles:

Koplik spots
CDC

Measles is a highly contagious viral disease transmitted by respiratory droplets. The incubation period (time from infection to the beginning of symptoms) is 10 to 12 days. Symptoms begin with a prodrome of fever, cough, coryza (inflammation of the nasal sinuses), and conjunctivitis (red eyes). These symptoms are easily confused with other upper respiratory infections. The prodromal stage is when a person infected with the measles virus is most contagious. Koplik spots are sores on the inside of the mouth that occur during this period and are considered pathognomonic for measles – meaning, if you have Koplik spots, you have the measles.

The prodromal stage lasts 2 to 4 days and ends with the onset of a rash that begins on the head and face, spreads to the trunk, and then the arms, legs, hands, and feet. The rash fades over 3 to 4 days in the same order as it appeared; face, trunk, extremities.

Complications of measles:

In industrialized countries, around 1% to 6% of people with measles with develop pneumonia, 7% to 9% will develop otitis media (ear infection), 8% will develop diarrhea, and 1 person out of 1,000 to 2,000 will develop encephalitis as the result of the infection.

Measles can cause severe disease and death in people with immune deficiencies, including people with HIV/AIDS, people on immune-suppressing drugs (e.g., cancer chemotherapy and drugs to prevent rejection of transplanted organs), and people with inherited immune disorders. Measles vaccine should not be given to people with severe immune disorders, so this is a population that is especially vulnerable to measles.

Before the introduction of measles vaccine, there were around 200,000 to 500,000 cases of measles every year in the U.S. As a result, there were approximately 150,000 cases of pneumonia, 100,000 cases of otitis media, 4,000 cases of encephalitis, and around 500 deaths caused by measles every year in the U.S.

Globally, the number of deaths due to measles has decreased from an estimated 2.6 million in 1980 to 535,000 in 2000 and 139,000 in 2008, most of which were children in developing countries. In addition to the complication listed above, measles commonly causes diarrhea, dehydration, and blindness in children in developing countries.

Subacute Sclerosing Panencephalitis (SSPE) is a rare but fatal complication of measles. It begins years after the initial measles infection with mental and behavioral changes, then progresses to myoclonic jerking, coma, and death. Jaxon's Cure is a website that tells the story of a boy who got the measles when he was too young to receive the vaccine, developed SSPE when he was 5 years old, and died two and a half years later.

Measles vaccine:

As I discussed in my post on pertussis vaccines, antibodies are transported across the placenta from mother to baby. The same is true of measles antibodies, which provides the newborn baby with some protection against measles in the first months of life. Unfortunately, these antibodies also interfere with baby's immune response to measles vaccines, which is why measles, mumps, and rubella vaccine (MMR) is given when babies are 12 to 15 months old - after maternal measles antibodies have cleared from the baby's blood. In countries where the risk of measles is high, measles vaccine is given at 9 months.

Like live attenuated influenza vaccine (LAIV), MMR is a live virus vaccine, so it should not be given to pregnant women because of the theoretical risk of infecting the unborn baby with vaccine virus. Measles infection during pregnancy can cause miscarriage and premature delivery, so women should be up-to-date on their MMR immunization before getting pregnant.

I've reached a point where I realize that there's still a lot to discuss and this post is already longer that I had anticipated. Besides, it's time for me to make an anniversary dinner for my bride.

More information:

• CDC's Travelers' Health: Measles Update
• Jaxon's Cure: Measles and Subacute Sclerosing Panencephalitis (SSPE)

References:

Centers for Disease Control and Prevention. (1998). Measles, mumps, and rubella – vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 47(8),1-57. http://www.cdc.gov/mmwr/preview/mmwrhtml/00053391.htm.

Centers for Disease Control and Prevention. (2012). Measles – United States, 2011. Morbidity and Mortality Weekly Report, 61(15), 253-257. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6115a1.htm.

Centers for Disease Control and Prevention. (2012). Progress in global measles control. Morbidity and Mortality Weekly Review, 61(4), 73-78. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6104a3.htm.

European Centre for Disease Prevention and Control. (2012). Surveillance report: European monthly measles monitoring. http://ecdc.europa.eu/en/publications/publications/sur_emmo_european-monthly-measles-monitoring-february-2012.pdf.

Gershon, A. A. (2009). Measles virus (rubeola). In Mandell, G. L., Bennett, J. E., & Dolin, R. (Eds.). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. (7th Ed.) [Electronic version].

National Institute of Neurological Disorders and Stroke. (2011). NINDS subacute sclerosing panencephalitis information page. http://www.ninds.nih.gov/disorders/subacute_panencephalitis/subacute_panencephalitis.htm.

Strebel, P. M., Papania, M. J., Dayan, G. H., & Halsey, N. A. (2008). Measles vaccine. In S. A. Plotkin, W. A. Orenstein, & P. A. Offit (Eds.) Vaccines (5th Ed.) [Electronic version]

World Health Organization. (2012). Measles. http://www.who.int/topics/measles/en.

Attack ratios

First: No vaccine is 100% effective.

For each vaccine, there is a proportion of people who will not develop immunity to the disease from the vaccine. Some vaccines are more effective than others. The effectiveness of pertussis vaccines is complicated by the fact that immunity to pertussis (whooping cough) wanes, so a person becomes more susceptible to Bordetella pertussis infection with the amount of time since the last dose of a pertussis-containing vaccine.

I know the last thing that U.S. taxpayers want to think about on April 15^th is math, but I found this sentence about the 2010 pertussis epidemic in California in the news recently: "Of the 132 patients under age 18, 81 percent were up to date on recommended whooping cough shots and eight percent had never been vaccinated. The other 11 percent had received at least one shot, but not the complete series."

Does that mean that pertussis vaccine is only 19% effective? Does that mean that children who have not been vaccinated are less likely to get pertussis?

The first thing to realize is that those are percentages of cases of pertussis, not percentages of vaccinated versus unvaccinated children who got pertussis.

The question is: what is the denominator?

To know how effective a vaccine is, the denominator we need is the number of vaccinated and unvaccinated people who were exposed to a vaccine-preventable disease.

In 2010, 95% of children 19 to 35 months of age had received at least 3 doses of pertussis-containing vaccine and 68% of children 13 – 17 years of age had received a dose of tetanus, diphtheria, and acellular pertussis vaccine (Tdap). In California, 93.1% of kindergarten students had received at least 3 doses of DTP/DTaP/DT.

The reason why more vaccinated children got pertussis than unvaccinated children is that most children are vaccinated against pertussis. The percent of vaccinated children who got pertussis (attack ratio) is smaller than the percent of unvaccinated children who got pertussis.

In large outbreaks, like the California pertussis epidemic and our current pertussis epidemic in Washington State, knowing the total number of people exposed to the infecting pathogen can be difficult, so let's look at some smaller outbreaks of another vaccine-preventable disease:

There was an outbreak of measles in a high school in Utah in 1996. Of the 17 cases of measles, 8 were in students who had received measles, mumps, and rubella vaccine (MMR) and 9 were in unvaccinated children. So, 47% of cases were vaccinated students and 53% of cases were unvaccinated students.

Does that mean that the vaccine was not effective?

Not when we consider that the denominators were 852 vaccinated students and 27 unvaccinated students in the school. So, the measles attack ratio* was 1% of vaccinated students (8 ÷ 852) and 33% of unvaccinated students (9 ÷ 27).

Vaccine effectiveness (VE) is calculated as:

[(ARU – ARV) ÷ ARU] x 100

where ARU is the attack ratio in unvaccinated individuals and ARV is the attack ratio in vaccinated individuals. In the Utah outbreak, the effectiveness of MMR at preventing measles was:

[(33 – 1) ÷ 33] x 100 = 97%

This outbreak occurred before the Advisory Committee on Immunization Practices (ACIP) recommended 2 doses of MMR rather than one. None of the 72 students who had received 2 doses of MMR got the measles, so the vaccine effectiveness for 2 doses of MMR was 100%.

Similar attack ratios and vaccine effectiveness has been seen in other measles outbreaks:

In an outbreak in a German public school, the measles attack ratio was:

·       53% of unvaccinated students

·       1.4% of vaccinated students

Vaccine effectiveness was:

·       98.1% for one dose of measles-containing vaccine

·       99.4% for two doses

In a primary school in Singapore, the measles attack ratio was:

·       52.8% of unvaccinated students

·       1.2% of vaccinated students

Vaccine effectiveness was 97.8%

What about pertussis?

In an outbreak in the Virgin Islands, the attack ratio for pertussis was:

·       18% of unvaccinated students

·       6% of vaccinated students

Vaccine effectiveness was 65.6%

Among pertussis cases ages 6 months to 5 years in an outbreak in an Amish community:

·       88 (72%) had no record of pertussis immunization

·       6 (5%) had received one or two doses of DTP/DTaP

·       29 (24%) had received ≥3 doses of DTP/DTaP

We don't know the denominators for this outbreak (the number of children exposed to B. pertussis), so we can't calculate the attack ratios or vaccine effectiveness.

Obviously, pertussis vaccines are not as effective as measles vaccine, but people vaccinated against pertussis that become infected with B. pertussis less likely than people who are not vaccinated to have severe disease and less likely to transmit the bacteria to others (Baptista et al., 2006; Préziosi & Halloran, 2003).

Why use a vaccine that is not 100% effective?

Would you stop locking your doors because burglars can still break into your house when the doors are locked? Would you stop wearing a seatbelt because you can still be injured in a motor vehicle accident while you are wearing a seatbelt?

Seatbelts reduce the risk serious injuries.

Locked doors reduce the risk of being robbed.

Vaccines reduce the risk of vaccine-preventable diseases.

Please drive carefully.

Road Crash Fatalities on US Income Tax Days

ማቴዎስ ጳውሎስ

*The term "attack rate" is commonly used, but a rate is an incidence over time.

References:

Baptista, P. N., Magalhães, V., Rodrigues, L. C., Rocha, M. A. W., & Pimentel, A. M. (2006). Pertussis vaccine effectiveness in reducing clinical disease, transmissibility, and proportion of case with positive culture after household exposure in Brazil. Pediatric Infectious Disease Journal, 25(9), 844-846. http://www.ncbi.nlm.nih.gov/pubmed/16940847.

Centers for Disease Control and Prevention. (1997). Measles outbreak, southwestern Utah, 1996. Morbidity and Mortality Weekly Report, 46(33), 766-769. http://www.cdc.gov/mmwr/preview/mmwrhtml/00049048.htm.

Centers for Disease Control and Prevention. (1998). Measles, mumps, and rubella – vaccine use and strategies for elimination of measles, mumps, rubella, and congenital rubella syndrome and control of mumps_ recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 47(8), 1-57. http://www.cdc.gov/mmwr/preview/mmwrhtml/00053391.htm.

Centers for Disease Control and Prevention. (2006). Pertussis outbreak in an Amish community – Kent County, Delaware, September 2004 – February 2005. Morbidity and Mortality Weekly Report, 55(30), 817-821. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5530a1.htm.

Centers for Disease Control and Prevention. (2011). National and state vaccination coverage among adolescents aged 13 through 17 years – United States, 2010. Morbidity and Mortality Weekly Report, 60(33),1117-1123. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6033a1.htm.

Centers for Disease Control and Prevention. (2011). National and state vaccination coverage among children aged 19 – 35 months – United States, 2010. Morbidity and Mortality Weekly Report, 60(34), 1157-1163. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6034a2.htm.

Centers for Disease Control and Prevention. (2011). Vaccination coverage among children in Kindergarten – United States, 2009 – 2010 school year. Morbidity and Mortality Weekly Report, 60(21), 700-704. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6021a4.htm.

Grens, K. (April 3, 2012). Whooping cough vaccine fades in pre-teens: study. Reuters Health Information. Retrieved April 14, 2012 from http://www.nlm.nih.gov/medlineplus/news/fullstory_123698.html.

Ong, G., Rasidah, N., Wan, S., & Cutter, J. (2007). Outbreak of measles in primary school students with high first dose MMR vaccination coverage. Singapore Medical Journal, 48(7), 656-661. http://smj.sma.org.sg/4807/4807a10.pdf.

Préziosi, M-P. & Halloran, M. E. (2003). Effects of pertussis vaccination on disease: vaccine efficacy in reducing clinical severity. Clinical Infectious Diseases, 37(6), 772-779. http://cid.oxfordjournals.org/content/37/6/772.long.

Wei, S. C., Tatti, K., Cushing, K., Rosen, J., Brown, K., Cassiday, P., Clark, T. et al. (2010). Effectiveness of adolescent and adult tetanus, reduced-dose diphtheria, and acellular pertussis vaccine against pertussis. Clinical Infectious Diseases, 51(3), 315-321. http://cid.oxfordjournals.org/content/51/3/315.long.

Wichmann, O., Hellenbrand, W. Sagebiel, D., Santibanez, S., Ahlemeyer, G., Vogt, G. et al. (2007). Large measles outbreak at a German public school, 2006. Pediatric Infectious Disease Journal, 26(9), 782-786. http://www.ncbi.nlm.nih.gov/pubmed/17721371.