Sandbox:Pertussis primary prevention

# Overview
Childhood vaccination is highly effective in preventing pertussis. Routine childhood vaccination in the United States is performed with the DTaP vaccine (acellular pertussis vaccine combined with tetanus and diphtheria toxoids).

# Vaccines
Use of Acellular Pertussis Vaccines Among Infants and Young Children Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Concerns about the safety of whole-cell pertussis vaccines prompted development of acellular vaccines that are less likely to provoke adverse events because they contain purified antigenic components of Bordetella pertussis. Two diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines ACEL-IMUNE{Registered} and Tripedia{Registered} have been licensed for several years, but (until recently) only for administration of the fourth and fifth doses in the series to children aged 15 months-6 years who previously had received three or more doses of diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine. Published reports indicate that, when administered to infants aged 2, 4, and 6 months, acellular pertussis vaccines are effective in preventing pertussis disease and associated with fewer local, systemic, and certain more serious adverse events than whole-cell pertussis vaccines. On the basis of these data, the Food and Drug Administration (FDA) has licensed three DTaP vaccines for use among children aged 6 weeks-6 years. Tripedia{Registered} is now licensed for the initial four doses, and ACEL-IMUNE{Registered} for all five doses of the diphtheria, tetanus and pertussis vaccination series. A third DTaP vaccine (Infanrix TM)  was licensed in January 1997 for the initial four doses of the series. Tripedia{Registered}, ACEL-IMUNE{Registered}, and Infanrix TM are now recommended for routine vaccination of infants and young children, although whole-cell pertussis vaccines remain acceptable alternatives. Tripedia{Registered}, ACEL-IMUNE{Registered}, and Infanrix TM are recommended for all remaining doses in the schedule for children who have started the vaccination series with one, two, three, or four doses of whole-cell pertussis vaccines. In September 1996, FDA licensed the use of TriHIBit TM (ActHIB{Registered} reconstituted with Tripedia{Registered})for the fourth dose in the series of vaccinations against diphtheria, tetanus, pertussis, and Haemophilus influenzae type b disease.
This statement a) provides general information regarding whole-cell pertussis vaccines currently licensed in the United States; b) summarizes results of recent studies of the immunogenicity, efficacy, and safety of acellular pertussis vaccines administered to infants and young children; c) presents recommendations for the use of Tripedia{Registered}, TriHIBit TM, ACEL-IMUNE{Registered}, and Infanrix TM vaccines; and d) supplements previous recommendations on pertussis vaccination.

## Whole-Cell Pertussis Vaccines
Four diphtheria and tetanus toxoids combined with whole-cell pertussis (DTP) vaccines are presently licensed for use in the United States. Vaccines of this type, prepared from suspensions of inactivated Bordetella pertussis bacterial cells, have been licensed for routine vaccination of infants since the mid-1940s. Based on controlled efficacy trials conducted in the 1940s and on subsequent observational efficacy studies, a primary series comprising four doses of whole-cell DTP vaccine is considered 70%-90% effective in preventing serious pertussis disease.
Whole-cell DTP vaccines are commonly associated with several local adverse events (e.g., erythema, swelling, and pain at the injection site), fever, and other mild systemic events (e.g., drowsiness, fretfulness, and anorexia). More severe systemic events (e.g., convulsions {with or without fever} and hypotonic hyporesponsive episodes) occur less frequently (ratio of one case to 1,750 doses administered) among children who receive whole-cell DTP vaccine. Acute encephalopathy occurs even more rarely (ratio of 0-10.5 cases to one million doses administered). Experts disagree on whether whole-cell pertussis vaccine causes lasting brain damage, but agree that if the vaccine causes such damage it does so only rarely. Concerns about safety prompted the development of more purified (acellular) pertussis vaccines that are associated with a lower frequency of adverse events and are effective in preventing pertussis disease.

## History of pertussis vaccine development
Infection with pertussis induces immunity, but not lasting protective immunity, and a second attack is possible.
Efforts to develop an inactivated whole-cell pertussis vaccine began soon after B. pertussis was grown in pure culture in 1906.  In 1925, the Danish physician Thorvald Madsen was the first to test a whole-cell pertussis vaccine on a wide scale. He used the vaccine to control outbreaks in the Faroe Islands in the North Sea.  In 1942, the American scientist Pearl Kendrick combined the whole-cell pertussis vaccine with diphtheria and tetanus toxoids to generate the first DTP combination vaccine.  To minimize the frequent side effects caused by the pertussis component of the vaccine, the Japanese scientist Yugi Sato developed an acellular pertussis vaccine consisting of filamentous hemagglutinin (FHA) and pertussis toxin (PT), which are secreted by B. pertussis into the culture medium.  Sato's acellular pertussis vaccine was used in Japan beginning in 1981. Later versions of the acellular pertussis vaccine used in other countries consisted of additional defined components of B. pertussis and were often part of the DTaP combination vaccine.

## Current status of pertussis vaccines
Pertussis vaccines are highly effective, strongly recommended, and save many infant lives every year.  Though the protection they offer lasts only a few years, they are given so that immunity lasts through childhood, the time of greatest exposure and greatest risk. The immunizations are given in combination with tetanus and diphtheria immunizations, at ages 2, 4, and 6 months, and later at 1518 months and 46 years and 11 years.
The short term effectiveness of the vaccines and the presence of B. pertussis infection in adults and adolescents who may transmit the bacteria to infants have caused many in the medical field to call for booster immunizations at later ages.  Although Canada, France, the U.S. and Germany now have approved booster shots for adolescents, adults, or both, other countries adhere to the tradition of discontinuing pertussis vaccination after the age of seven, from concerns that there are side effects associated with the first available "whole-cell" pertussis immunizations that tended to increase with age. The whole-cell vaccine is still used in poor countries, since it is cheaper than the newer and safer acellular formulation.
As the immunity from infection or vaccination lasts only a few years, the discontinuation of booster vaccination in older persons caused the emergence of a large pool of older persons lacking immunity, followed by an increase of adult-onset pertussis that accelerated beginning in about 2004.  This burgeoning outbreak is predicted to increasingly infect adults and adolescents with debilitating cases, but poses even more serious public health dangers to newborns.  As adolescent and adult cases surge, newborns are again at risk of exposure to pertussis circulating in adolescents or adults in the community before the infants' vaccinations can be completed.
The decision to resume vaccinating teens and adults reflects in part that the newer acellular vaccine, known as DTaP, has greatly reduced the incidence of adverse effects observed with the earlier "whole-cell" pertussis vaccine. An acellular vaccine preparation for adults and adolescents has been approved in Canada, Europe, and the United States. In the U.S., the Food and Drug Administration has authorized both the use of the vaccines Boostrix (GlaxoSmithKline) for 10-18 year olds in May 2005 and Adacel (Sanofi Pasteur) for 11-64 year olds in August 2005.  These vaccines are recommended for all teens and adults within the indicated age ranges, except for those with a history of adverse reaction to the whole-cell pertussis vaccines. The most serious side-effects of traditional "whole-cell" pertussis immunizations were neurological: and included seizures and hypotonic episodes.

## Whole-cell pertussis vaccine controversy
Much of the controversy surrounding the DTP vaccine in the 1970s and 1980s related to the question of whether the whole-cell pertussis component caused permanent brain injury in rare cases.  Although it was well-established that the pertussis component of the DTP vaccine accounted for most of the minor local and systemic side effects in many vaccinated infants, several published studies failed to show a causal relationship between administration of the DTP vaccine and permanent brain injury. However, criticism of these studies and well-publicized anecdotal reports of DTP-induced permanent disability and death gave rise to anti-DTP movements.
By the late 1970s, publicity about adverse reactions and deaths following pertussis vaccination caused the immunization rate to fall in several countries, including Great Britain, Sweden, and Japan.  In many cases, a dramatic increase in the incidence of pertussis followed. These developments led Yugi Sato to introduce a safer acellular version of the pertussis vaccine for Japan in 1981.  Nevertheless, other countries continued to use the whole-cell DTP formulation.
In the United States, low profit margins and an increase in vaccine-related lawsuits led many manufacturers to stop producing the DTP vaccine by the early 1980s. In 1982, the television documentary "DTP: Vaccine Roulette" depicted the lives of children whose severe disabilities were blamed on the DTP vaccine.  The negative publicity generated by the documentary led to a tremendous increase in the number of lawsuits filed against vaccine manufacturers.  By 1985, manufacturers of vaccines had difficulty obtaining liability insurance.  The price of the DTP vaccine skyrocketed, leading to shortages around the country.  Only one manufacturer of the DPT vaccine remained in the U.S. by the end of 1985.  To avert a vaccine crisis, Congress in 1986 passed the National Childhood Vaccine Injury Act (NCVIA), which established a federal no-fault system to compensate victims of injury caused by mandated vaccines. Since then, the prices of vaccines have stabilized, and the number of lawsuits filed against DTP manufacturers has dwindled.  The majority of claims that have been filed through the NCVIA have been related to injuries allegedly caused by the whole-cell DTP vaccine.  The acellular pertussis vaccine was approved in the United States in 1992 for use in the combination DTaP vaccine. Research has shown the acellular vaccine to be safe, with few reports of adverse effects. Although the whole-cell DTP vaccine is no longer used in the United States, it is still purchased by the World Health Organization and distributed to developing nations because of its much reduced cost compared to the acellular DTaP vaccine.

# Prevention in Close Contacts
- Close contacts who receive appropriate antibiotics (chemoprophylaxis) during the 721 day incubation period may be protected from developing symptomatic disease.  Close contacts are defined as anyone coming into contact with the respiratory secretions of an infected person in the 21 days before or after the infected person's cough began.
- Close contacts should be administered a course of antibiotics within 3 weeks of exposure, especially in high-risk settings; same doses as in treatment schedule.
- The recommended antimicrobial agents for treatment or chemoprophylaxis of pertussis are azithromycin, clarithromycin and erythromycin. Trimethoprim-sulfamethoxasole can also be used.

## Infants

### Age 1 Month
- Erythromycin, clarithromycin, and azithromycin are preferred for the post exposure prophylaxis of pertussis in persons 1 month of age.
- For persons 2 months of age, an alternative to macrolides is trimethoprim-sulfamethoxazole.

### Age <1 Month
- For infants <1 month of age, azithromycin is preferred for post exposure prophylaxis and treatment because azithromycin has not been associated with infantile hypertrophic pyloric stenosis (IHPS), whereas erythromycin has.