Pertussis

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Pertussis
Pertussis.jpg
A young boy coughing due to pertussis.
Classification and external resources
Specialty Infectious disease
ICD-10 A37
ICD-9-CM 033
DiseasesDB 1523
MedlinePlus 001561
eMedicine emerg/394 ped/1778
Patient UK Pertussis
MeSH D014917
Orphanet 1489

Pertussis (also known as whooping cough or 100-day cough) is a highly contagious bacterial disease.[1][2] Initially, symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough. This is then followed by weeks of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in.[2] The coughing may last for 10 or more weeks, hence the phrase "100-day cough".[3] A person may cough so hard that they vomit, break ribs, or become very tired from the effort.[2][4] Children less than one year old may have little or no cough and instead have periods where they do not breathe.[2] The time between infection and the onset of symptoms is usually seven to ten days.[5] Disease may occur in those who have been vaccinated, but symptoms are typically milder.[2]

Pertussis is caused by the bacterium Bordetella pertussis.[6] It is an airborne disease which spreads easily through the coughs and sneezes of an infected person.[6][7] People are infectious to others from the start of symptoms until about three weeks into the coughing fits. Those treated with antibiotics are no longer infectious after five days.[8] Diagnosis is by collecting a sample from the back of the nose and throat. This sample can then be tested by either culture or by polymerase chain reaction.[9]

Prevention is mainly by vaccination with the pertussis vaccine.[10] Initial immunization is recommended between six and eight weeks of age, with four doses to be given in the first two years of life.[11] The vaccine becomes less effective over time, with additional doses often recommended for older children and adults.[12] Antibiotics may be used to prevent the disease in those who have been exposed and are at risk of severe disease.[13] In those with the disease, antibiotics are useful if started within three weeks of the initial symptoms, but otherwise have little effect in most people. In children less than one year old and among those who are pregnant, they are recommended within six weeks of symptom onset. Antibiotics used include erythromycin, azithromycin, clarithromycin, or trimethoprim/sulfamethoxazole.[8] Evidence to support interventions, other than antibiotics, for the cough is poor.[14] Many children less than a year of age require hospitalization.[2]

An estimated 16 million people worldwide are infected per year.[14] Most cases occur in the developing world, and people of all ages may be affected.[10][14] In 2013, it resulted in 61,000 deaths – down from 138,000 deaths in 1990.[15] Nearly 0.5% of infected children less than one year of age die.[4] Outbreaks of the disease were first described in the 16th century. The bacterium that causes the infection was discovered in 1906. The pertussis vaccine became available in the 1940s.[5]

Signs and symptoms[edit]

A boy with pertussis

The classic symptoms of pertussis are a paroxysmal cough, inspiratory whoop, and fainting, or vomiting after coughing.[16] The cough from pertussis has been documented to cause subconjunctival hemorrhages, rib fractures, urinary incontinence, hernias, and vertebral artery dissection.[16] Violent coughing can cause the pleura to rupture, leading to a pneumothorax. Vomiting after a coughing spell or an inspiratory whooping sound on coughing, almost doubles the likelihood that the illness is pertussis. The absence of a paroxysmal cough or posttussive emesis, though, makes it almost half as likely.[16]

The illness usually starts with mild respiratory symptoms, mild coughing, sneezing, or a runny nose. This is known as the catarrhal stage. After one to two weeks, the coughing classically develops into uncontrollable fits, each with five to ten forceful coughs, followed by a high-pitched "whoop" sound in younger children, or a gasping sound in older children, as the person tries to inhale (paroxysmal stage).

Coughing fits can occur on their own or can be triggered by yawning, stretching, laughing, eating, or yelling; they usually occur in groups, with multiple episodes on an hourly basis throughout the day. This stage usually lasts two to eight weeks, or sometimes longer. A gradual transition then occurs to the convalescent stage, which usually lasts one to four weeks. This stage is marked by a decrease in paroxysms of coughing, both in frequency and severity, and a cessation of vomiting. A tendency to produce the "whooping" sound after coughing may remain for a considerable period after the disease itself has cleared up.

Incubation period[edit]

The time between exposure and the development of symptoms is on average 7–14 days (range 6–20 days),[17] rarely as long as 42 days.[18]

Cause[edit]

Pertussis is caused by the bacterium Bordetella pertussis. It is an airborne disease which spreads easily through the coughs and sneezes of an infected person.[6]

Spread from animals[edit]

Uncertainties have existed of B. pertussis and whooping cough as a zoonotic disease since around 1910[19][20] but in the 1930s, knowledge was gained that the bacteria lost their virulent power when repeatedly spread on agar media. This explained the difficulties to reproduce results from different studies as the pre-inoculating handlings of the bacteria were not standardized among scientists.[21]

Today it is established that at least some primate species are highly susceptible to B. pertussis and develop clinical whooping cough in high incidence when exposed to low inoculation doses.[22][23] The bacteria may be present in wild animal populations, but this is not confirmed by laboratory diagnosis, although whooping cough is known among wild gorillas.[24] Several zoos also have a long-standing custom of vaccinating their primates against whooping cough.[25]

Diagnosis[edit]

Gram stain of Bordetella pertussis

A complete blood count is usually ordered. Lymphocytosis is a diagnostic clue for pertussis, although not specific.

Methods used in laboratory diagnosis include culturing of nasopharyngeal swabs on a nutrient medium (Bordet-Gengou medium), polymerase chain reaction (PCR), direct fluorescent antibody (DFA), and serological methods (e.g. complement fixation test).[26] The bacteria can be recovered from the person 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.

Serology may be used for adults and adolescents who have already been infected for several weeks to determine whether antibody against pertussis toxin or another virulence factor of B. pertussis is present at high levels in the blood of the person.[27] By this stage, they have been contagious for some weeks and may have spread the infection to many people. Because of this, adults, who are not in great danger from pertussis, are increasingly being encouraged to be vaccinated.

A similar, milder disease is caused by B. parapertussis.[28]

Prevention[edit]

The primary method of prevention for pertussis is vaccination. Evidence is insufficient to determine the effectiveness of antibiotics in those who have been exposed, but are without symptoms.[29] Preventive antibiotics, however, are still frequently used in those who have been exposed and are at high risk of severe disease (such as infants).[10]

Vaccine[edit]

Pertussis vaccines are effective at preventing illness[30] and are recommended for routine use by the World Health Organization[31] and the Centers for Disease Control and Prevention.[32] The vaccine saved an estimated half a million lives in 2002.[31]

The multicomponent acellular pertussis vaccine is 71–85% effective, with greater effectiveness for more severe strains.[30] Despite widespread vaccination, however, pertussis has persisted in vaccinated populations and is today "one of the most common vaccine-preventable diseases in Western countries".[33] The 21st-century resurgences in pertussis infections are attributed to a combination of waning immunity and bacterial mutations that elude vaccines.[33][34]

Immunization does not confer lifelong immunity; a 2011 CDC study indicated that protection may only last three to six years. This covers childhood, which is the time of greatest exposure and greatest risk of death from pertussis.[16][35]

An effect of widespread immunization on society has been the shift of reported infections from children aged 1–9 years to infants, adolescents, and adults, with adolescents and adults acting as reservoirs for B. pertussis and infecting infants with fewer than three doses of vaccine.[36]

Infection induces incomplete natural immunity that wanes over time.[37] A 2005 study said estimates of the duration of infection-acquired immunity range from 7 to 20 years and the different results could be the result of differences in levels of circulating B. pertussis, surveillance systems, and case definitions used. The study said protective immunity after vaccination wanes after 4–12 years.[38] Vaccination exemption laws appear to increase cases.[39][40]

Both WHO and the CDC found that the acellular pertussis vaccines were effective at prevention of the disease, but had a limited impact on infection and transmission, meaning that vaccinated people could act as asymptomatic reservoirs of infection.[41][42]

Treatment[edit]

The antibiotics erythromycin, clarithromycin, or azithromycin are typically the recommended treatment.[29] Newer macrolides are frequently recommended due to lower rates of side effects.[10] Trimethoprim-sulfamethoxazole (TMP/SMX) may be used in those with allergies to first-line agents or in infants who have a risk of pyloric stenosis from macrolides.[10]

A reasonable guideline is to treat people age >1 year within 3 weeks of cough onset and infants age <1 year and pregnant women within 6 weeks of cough onset. If the person is diagnosed late, antibiotics will not alter the course of the illness, and even without antibiotics, they should no longer be spreading pertussis.[10] Antibiotics when used early decrease the duration of infectiousness, and thus prevent spread.[10] Short-term antibiotics (azithromycin for 3–5 days) are as effective as long-term treatment (erythromycin 10–14 days) in eliminating B. pertussis with fewer and less severe side effects.[43]

People with pertussis are infectious from the beginning of the catarrhal stage (a runny nose, sneezing, low-grade fever, symptoms of the common cold) through the third week after the onset of paroxysms (multiple, rapid coughs) or until 5 days after the start of effective antimicrobial treatment.

Effective treatments of the cough associated with this condition have not been developed.[44]

Prognosis[edit]

Disability-adjusted life year for pertussis per 100,000 inhabitants as of 2004.
  No data
  Less than 50
  50–100
  100–150
  150–200
  200–250
  250–300
  300–350
  350–400
  400–450
  450–500
  500–550
  More than 550

Common complications include pneumonia, bronchitis, encephalopathy, earache, and seizures. Most healthy older children and adults fully recover, but those with comorbid conditions have a higher risk of morbidity and mortality.

Infection in newborns is particularly severe. Pertussis is fatal in an estimated 1.6% of hospitalized US infants under one year of age.[45] First-year infants are also more likely to develop complications, such as: pneumonia (20%), encephalopathy (0.3%), seizures (1%), failure to thrive, and death (1%)[45]—perhaps due to the ability of the bacterium to suppress the immune system.[46] Pertussis can cause severe paroxysm-induced cerebral hypoxia, and 50% of infants admitted to hospital suffer apneas.[45] Reported fatalities from pertussis in infants increased substantially from 1990 to 2010.[47]

Epidemiology[edit]

Whooping cough deaths per million persons in 2012
  0–0
  1–1
  2–3
  4–4
  5–5
  6–32
  33–38
  39–44
  45–79

Worldwide, whooping cough affects 48.5 million people yearly.[48][needs update] One estimate for 2013 stated it resulted in about 61,000 deaths – down from 138,000 deaths in 1990.[15] Another estimated 195,000 child deaths yearly from the disease worldwide.[49] This is despite generally high coverage with the DTP and DTaP vaccines. Pertussis is one of the leading causes of vaccine-preventable deaths worldwide.[50] About 90% of all cases occur in developing countries.[50]

Before vaccines, an average of 178,171 cases was reported in the U.S., with peaks reported every two to five years; more than 93% of reported cases occurred in children under 10 years of age. The actual incidence was likely much higher. After vaccinations were introduced in the 1940s, pertussis incidence fell dramatically to less than 1,000 by 1976. Incidence rates have increased since 1980. In 2012, rates in the United States reached a high of 41,880 people; this is the highest it has been since 1955 when numbers reached 62,786.[51]

Pertussis is the only vaccine-preventable disease that is associated with increasing deaths in the U.S. The number of deaths increased from four in 1996 to 17 in 2001, almost all of which were infants under one year.[52] In Canada, the number of pertussis infections has varied between 2,000 and 10,000 reported cases each year over the last ten years, and it is the most common vaccine-preventable illness in Toronto.[53]

In 2009 Australia reported an average of 10,000 cases a year, and the number of cases had increased.[54] In the U.S. pertussis in adults has increased significantly since about 2004.[55]

US outbreaks[edit]

An epidemiologist tests blood samples for pertussis during a 2010 outbreak.

In 2010 ten infants in California died, and health authorities declared an epidemic encompassing 9,120 cases.[56][57] They found that doctors had failed to correctly diagnose the infants' condition during several visits.[58] Statistical analysis identified significant overlap in communities with a cluster of nonmedical child exemptions and cases. The number of exemptions varied widely among communities, but tended to be highly clustered. In some schools, more than three-fourths of parents filed for vaccination exemptions. The data suggest vaccine refusal based on nonmedical reasons and personal belief exacerbated the outbreak. Other factors included reduced duration of the current vaccine and that most vaccinated adults and older children had not received a booster shot.[59][60]

In April and May 2012 pertussis was declared to be at epidemic levels in Washington, with 3,308 cases.[61][62][63] In December 2012 Vermont declared an epidemic of 522 cases.[64] Wisconsin had the highest incidence rate, with 3,877 cases, although it did not make an official epidemic declaration.[63]

History[edit]

Discovery[edit]

B. pertussis was discovered in 1906 by Jules Bordet and Octave Gengou, who also developed the first serology and vaccine. Efforts to develop an inactivated whole-cell vaccine began soon after B. pertussis was cultured that year. In the 1920s, Louis W. Sauer developed a weak vaccine for whooping cough at Evanston Hospital (Evanston, IL). In 1925 Danish physician Thorvald Madsen was the first to test a whole-cell vaccine on a wide scale.[65] Madsen used the vaccine to control outbreaks in the Faroe Islands in the North Sea.

Vaccine[edit]

In 1932 an outbreak of whooping cough hit Atlanta, Georgia, prompting pediatrician Leila Denmark to begin her study of the disease. Over the next six years her work was published in the Journal of the American Medical Association, and in partnership with Emory University and Eli Lilly & Company, she developed the first pertussis vaccine.[66] In 1942 American scientists Grace Eldering, Loney Gordon, and Pearl Kendrick combined the whole-cell pertussis vaccine with diphtheria and tetanus toxoids to generate the first DTP combination vaccine.[67] To minimize the frequent side effects caused by the pertussis component, Japanese scientist Yuji Sato developed an acellular vaccine consisting of purified haemagglutinins (HAs: filamentous strep throat and leucocytosis-promoting-factor HA), which are secreted by B. pertussis. Sato's acellular pertussis vaccine was used in Japan starting in 1981.[68] Later versions of the acellular vaccine in other countries consisted of additional defined components of B. pertussis and were often part of the DTaP combination vaccine.

Controversy[edit]

In the 1970s and 1980s, a controversy erupted related to the question of whether the whole-cell pertussis component caused permanent brain injury in rare cases, called pertussis vaccine encephalopathy. Despite this allegation, doctors recommended the vaccine due to the overwhelming public health benefit, because the claimed rate was very low (one case per 310,000 immunizations, or about 50 cases out of the 15 million immunizations each year in the United States), and the risk of death from the disease was high (pertussis killed thousands of Americans each year before the vaccine was introduced).[69]

No studies showed a causal connection, and later studies showed no connection of any type between the DPT vaccine and permanent brain injury. The alleged vaccine-induced brain damage proved to be an unrelated condition, infantile epilepsy.[70] In 1990, the Journal of the American Medical Association called the connection a "myth" and "nonsense".[71]

However, before that point, criticism of the studies showing no connection and a few well-publicized anecdotal reports of permanent disability that were blamed on the DPT vaccine gave rise to 1970s anti-DPT movements.[72] Negative publicity and fear-mongering caused the immunization rate to fall in several countries, including the UK, Sweden, and Japan. A dramatic increase in the incidence of pertussis followed.[73]

In the United States, low profit margins and an increase in vaccine-related lawsuits led many manufacturers to stop producing the DPT vaccine by the early 1980s.[69] In 1982, the television documentary DPT: Vaccine Roulette depicted the lives of children whose severe disabilities were incorrectly blamed on the DPT vaccine by reporter Lea Thompson.[74] The ensuing negative publicity led to many lawsuits against vaccine manufacturers.[75] By 1985, vaccine manufacturers had difficulty obtaining liability insurance. The price of DPT vaccine skyrocketed, leading providers to curtail purchases, limiting availability. Only one manufacturer remained in the US by the end of 1985. To correct the situation, 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.[76] The majority of claims that have been filed through the NCVIA have been related to injuries allegedly caused by the whole-cell DPT vaccine.

The concerns about side effects led Sato to introduce an even safer acellular vaccine for Japan in 1981 that was approved in the US in 1992 for use in the combination DTaP vaccine. The acellular vaccine has a rate of adverse events similar to that of a Td vaccine (a tetanus-diphtheria vaccine containing no pertussis vaccine).[77]

The complete B. pertussis genome of 4,086,186 base pairs was published in 2003.[78]

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