Pertussis

Pertussis, also known as whooping cough, a highly contagious disease caused by the bacterium, Bordetella pertussis; it derived its name from a characteristic severe hacking cough followed by intake of breath that sounds like 'whoop'; a similar, milder disease is caused by B. parapertussis.^[1] Although many medical sources describe the whoop as "high-pitched," this is generally the case with infected babies and children only, not adults. [1] Worldwide, there are 30–50 million pertussis cases and about 300,000 deaths per year. Despite generally high coverage with the DTP and DTaP vaccines, pertussis is one of the leading causes of vaccine-preventable deaths world-wide. Most deaths occur in young infants who are either unvaccinated or incompletely vaccinated; three doses of the vaccine are necessary for complete protection against pertussis. Ninety percent of all cases occur in the developing world. However, in the winter of 2006, a New York school district [2] suffered a large pertussis outbreak with thirteen plus students falling victim to the infection. [3] Also in the fall of 2006, a pertussis outbreak struck New Trier High School, a public school in Winnetka, Illinois, with twenty-four high school students catching the disease. In response, the Cook County Department of Public Health provided vaccine, free of charge, to eligible students. As of November 2007, a new outbreak of pertussis has afflicted nearly 50 students in the Worthington, Ohio school district [4] and 35-40 students at Bob Jones University in South Carolina [5].

Pertussis was recognizably described as early as 1578 by Guillaume de Baillou (1538-1616), but earlier reports date back at least to the 12th century.^[2] B. pertussis was isolated in pure culture in 1906 by Jules Bordet and Octave Gengou, who also developed the first serology and vaccine. The complete B. pertussis genome of 4,086,186 base pairs was sequenced in 2002.

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Characterization

After a two day incubation period, pertussis in infants and young children is characterized initially by mild respiratory infection symptoms such as cough, sneezing, and runny nose (catarrhal stage). After one to two weeks, the cough changes character, with paroxysms of coughing followed by an inspiratory "whooping" sound (paroxysmal stage). Coughing fits may be followed by vomiting due to the sheer violence of the fit. In severe cases, the vomiting induced by coughing fits can lead to malnutrition. The fits that do occur on their own can also be triggered by yawning, stretching, laughing, or yelling. Coughing fits gradually diminish over one to two months during the convalescent stage. Other complications of the disease include pneumonia, encephalitis, pulmonary hypertension, and secondary bacterial superinfection.^[3].

Because neither vaccination nor infection confers long-term immunity, infection of adolescents and adults is also common ^[4] Most adults and adolescents who become infected with Bordetella pertussis have been vaccinated or infected years previously. When there is residual immunity from previous infection or immunization, symptoms may be milder, such as a prolonged cough without the other classic symptoms of pertussis. Nevertheless, infected adults and adolescents can transmit the bacteria to susceptible individuals. Adults and adolescent family members are the major source of transmission of the bacteria to unimmunized or partially immunized infants, who are at greatest risk of severe complications from pertussis.

Transmission and Diagnosis

Adults and adolescents are the primary reservoir for pertussis. Pertussis is spread by contact with airborne discharges from the mucous membranes of infected people, who are most contagious during the catarrhal stage. Because the symptoms during the catarrhal stage are nonspecific, pertussis is usually not diagnosed until the appearance of the characteristic cough of the paroxysmal stage. Methods used in laboratory diagnosis include culturing of nasopharyngeal swabs on Bordet-Gengou medium, polymerase chain reaction (PCR), immunofluorescence (DFA), and serological methods. The bacteria can be recovered from the patient only during the first three weeks of illness, rendering culturing and DFA useless after this period, although PCR may have some limited usefulness for an additional three weeks. For most adults and adolescents, who often do not seek medical care until several weeks into their illness, serology is often used to determine whether antibody against pertussis toxin or another component of B. pertussis is present at high levels in the blood of the patient.

Treatment

Treatment with an effective antibiotic (erythromycin or azithromycin) shortens the infectious period but does not generally alter the outcome of the disease; however, when treatment is initiated during the catarrhal stage, symptoms may be less severe. Three macrolides, erythromycin, azithromycin and clarithromycin are used in the U.S. for treatment of pertussis; trimethoprim-sulfamethoxazole is generally used when a macrolide is ineffective or is contraindicated. Close contacts who receive appropriate antibiotics (chemoprophylaxis) during the 7–21 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.

Vaccines

History of pertussis vaccine development

Infection with pertussis induces immunity, but not lasting protective immunity, and a second attack is possible.^[5] Efforts to develop an inactivated whole-cell pertussis vaccine began soon after B. pertussis was grown in pure culture in 1906. In the 1920's Dr. Louis Sauer develops a vaccine for whooping cough at Evanston Hospital (Chicago, IL). In 1925, the Danish physician Thorvald Madsen was the first to test a whole-cell pertussis vaccine on a wide scale.<^[6] 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 Yuji Sato developed an acellular pertussis vaccine consisting of purified haemagglutinins (HAs: filamentous HA and leucocytosis-promoting-factor HA), which are secreted by B. pertussis into the culture medium. Sato's acellular pertussis vaccine was used in Japan since the autumn of 1981.^[7] 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.^[8] The immunizations are given in combination with tetanus and diphtheria immunizations, at ages 2, 4, and 6 months, and later at 15–18 months and 4–6 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.^{[citation needed]} 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. ^[9] 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.^[10] 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.^[11]

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.^[12] These developments led Yuji 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.^{[citation needed]} 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.^[13] 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.^[14] 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.[6] 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.

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