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Whooping cough
SpecialtyInfectious diseases Edit this on Wikidata

Pertussis—commonly called whooping cough (/ˈwuːpɪŋ/, /ˈhuːpɪŋ/, or /ˈhwuːpɪŋ kɒf/)—is a highly contagious bacterial disease caused by Bordetella pertussis. In some countries, this disease is called the 100 days' cough or cough of 100 days.[1]

Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air after coughing.[2] The coughing stage lasts approximately six weeks before subsiding.[citation needed] Prevention by vaccination is of primary importance given the seriousness of the disease in children.[3] Although treatment is of little direct benefit to the person infected, antibiotics are recommended because they shorten the duration of infectiousness.[3] It is currently estimated that the disease annually affects up to 50 million people, causing up to 300,000 deaths worldwide.[4]

Signs and symptoms

A boy with pertussis.

The classic symptoms of pertussis are a paroxysmal cough, inspiratory whoop, and fainting and/or vomiting after coughing.[5] The cough from pertussis has been documented to cause subconjunctival hemorrhages, rib fractures, urinary incontinence, hernias, post-cough fainting, and vertebral artery dissection.[5] Violent coughing can cause the pleura to rupture, leading to a pneumothorax. If there is vomiting after a coughing spell or an inspiratory whooping sound on coughing, the likelihood almost doubles that the illness is pertussis. On the other hand, the absence of a paroxysmal cough or posttussive emesis makes it almost half as likely.[5]

The incubation period is typically seven to ten days with a range of four to 21 days and rarely may be as long as 42 days,[6] after which there are usually mild respiratory symptoms, mild coughing, sneezing, or 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 patient struggles to breathe in afterwards (paroxysmal stage).

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 two 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.

Diagnosis

Gram stain of the bacteria Bordetella pertussis

Methods used in laboratory diagnosis include culturing of nasopharyngeal swabs on Bordet-Gengou medium, polymerase chain reaction (PCR), direct 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 may be 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. 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.[7]

Prevention

The primary method of prevention for pertussis is vaccination. There is insufficient evidence to determine the effectiveness of antibiotics in those who have been exposed but are without symptoms.[8] Preventative antibiotics, however, are still frequently used in those who have been exposed and are at high risk of severe disease (such as infants).[3]

Vaccine

Pertussis vaccines are effective.[9] It is routinely recommended by the World Health Organization[10] and the Center for Disease Control and Prevention,[11] with estimates that it has saved over half a million lives in 2002.[10]

The multi-component acellular pertussis vaccine, for example, is 71–85% effective with greater effectiveness for more severe disease.[9] Despite widespread use of the vaccine, however, pertussis has persisted in vaccinated populations and is today "one of the most common vaccine-preventable diseases in Western countries".[12] The recent resurgences in pertussis infections are attributed to a combination of waning immunity and new mutations in the bacteria that existing vaccines are unable to effectively control.[12][13]

Immunization against pertussis does not confer lifelong immunity; a 2011 study by the CDC indicated that the duration of 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.[5][14]

Infection with pertussis induces incomplete natural immunity that wanes over time.[15] Natural immunity lasts longer than vaccine-induced immunity, with one study reporting maximum effectiveness as long as 20 years in the former and 12 in the latter.[16] Vaccination exemption laws appear to result in increased cases.[17][18]

Management

The antibiotic erythromycin or azithromycin are typically the recommended treatment.[8] Newer macrolides are frequently recommended due to lower rates of side effects.[3] Trimethoprim-sulfamethoxazole (TMP-SMZ) may be used in those with allergies to first-line agents or in infants who have a risk of pyloric stenosis from macrolides.[3]

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.[3] Antibiotics when used early decrease the duration of infectiousness and thus prevent spread.[3] Short term antibiotics (azithromycin for 3–5 days) are as effective as long-term treatment (erythromycin 10–14 days) in eliminating B. pertussis with less side effects.[19]

People with pertussis are infectious from the beginning of the catarrhal stage (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.[20]

Prognosis

Common complications of the disease include pneumonia, encephalopathy, earache, or seizures.

Most healthy older children and adults will have a full recovery from pertussis, however those with comorbid conditions can have a higher risk of morbidity and mortality.

Infection in newborns is particularly severe. Pertussis is fatal in an estimated 1.6% of hospitalized infants who are under one year of age.[21] Infants under one are also more likely to develop complications, such as: pneumonia (20%), encephalopathy (0.3%), seizures (1%), failure to thrive, and death (1%)[21]—perhaps due to the ability of the bacterium to suppress immune response against it.[22] Pertussis can cause severe paroxysm-induced cerebral hypoxia and 50% of infants admitted to hospital will suffer apneas.[21] Reported fatalities from pertussis in infants have increased substantially over the past 20 years.[23]

Epidemiology

Disability-adjusted life year for pertussis per 100,000 inhabitants.
  1-14
  14-23
  25–50
  50–75
  75–100
  100–150
  150–200
  200–300
  300–400
  400–500
  500–600
  600–700
  ≥ 700

Worldwide, whooping cough affects 48.5 million people yearly.[24] In 2013 it resulted in about 61,000 deaths – down from 138,000 deaths in 1990.[25] This is despite generally high coverage with the DTP and DTaP vaccines. Pertussis is one of the leading causes of vaccine-preventable deaths world-wide.[26] 90% of all cases occur in developing countries.[26]

Before vaccines, an average of 178,171 cases were 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, 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.[27]

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.[28] 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's the most common vaccine preventable illness in Toronto.[29]

Australia reports an average of 10,000 cases a year, but the number of cases has increased in recent years.[30] In the U.S. pertussis in adults has increased significantly since about 2004.[31]

US outbreaks

In 2010 ten infants in California died and health authorities declared an epidemic with 9,120 cases.[32][33] Investigating the cases of the ten infant fatalities, it found that doctors had failed to correctly diagnose the infants' condition as Pertussis during the several early visits.[34] Statistical analysis identified significant overlap in communities with cluster of nonmedical exemptions for children and cases of whooping cough. The study found the number of exemption varies widely among communities but tends to be highly clustered, in some schools more than ¾ of parents filed for exemptions not to vaccinate their children. The data suggest vaccine refusal based on nonmedical reason and personal belief may have been one of several factors, in addition to less long lasting effect of the current vaccine and most vaccinated adults and older children have not received a booster shot, contributed to the California outbreak in 2010.[35][36]

In April and May 2012, pertussis was declared to be at epidemic levels in the US state of Washington with 3,308 cases by December.[37][38][39] In December 2012, the state of Vermont declared a pertussis epidemic with 522 cases.[40] The state of Wisconsin has the highest incidence rate, with 3,877 cases of whooping cough, however it did not release an official epidemic declaration.[39]

History

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 pertussis vaccine began soon after B. pertussis was grown in pure culture in 1906. In the 1920s, Louis W. Sauer developed a vaccine for whooping cough at Evanston Hospital (Evanston, IL), but this first vaccine was not very effective and thousands of children continued to die. In 1925, the Danish physician Thorvald Madsen was the first to test a whole-cell pertussis vaccine on a wide scale.[41]

Madsen used the vaccine to control outbreaks in the Faroe Islands in the North Sea. In 1942, the 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.[42] 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 strep throat and leucocytosis-promoting-factor HA), which are secreted by B. pertussis into the culture medium. Sato's acellular pertussis vaccine was used in Japan starting in 1981.[43] 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.

The complete B. pertussis genome of 4,086,186 base pairs was sequenced in 2004.[44]

Society and culture

Much of the controversy surrounding the DPT vaccine in the 1970s and 1980s related to the question of whether the whole-cell pertussis component caused permanent brain injury in rare cases, called pertussis vaccine encephalopathy. Despite this possibility, 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).[45]

No studies showed a causal connection, and later studies showed no connection of any type between administration of the DPT vaccine and permanent brain injury. The alleged vaccine-induced brain damage proved to be an unrelated condition, infantile epilepsy.[46] Eventually evidence against the hypothesized existence of pertussis vaccine encephalopathy mounted to the point that in 1990, the Journal of American Medical Association called it a "myth" and "nonsense".[47]

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 anti-DPT movements in the 1970s.[48] The negative publicity and fear-mongering caused the immunization rate to fall in several countries, including the UK, Sweden, and Japan. In many cases, a dramatic increase in the incidence of pertussis followed.[49]

Unscientific claims about the vaccine pushed suppliers of the vaccines out of the market.[45] 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.[45]

In 1982, the television documentary DPT: Vaccine Roulette depicted the lives of children whose severe disabilities were inaccurately blamed on the DPT vaccine by reporter Lea Thompson.[50] The negative publicity generated by the documentary led to a tremendous increase in the number of lawsuits filed against vaccine manufacturers.[51] By 1985, manufacturers of vaccines had difficulty obtaining liability insurance. The price of the DPT 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.[52] 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 Yuji Sato to introduce an even safer acellular version of the pertussis vaccine for Japan in 1981. The acellular pertussis vaccine was approved in the United States in 1992 for use in the combination DTaP vaccine. Research has shown that the acellular vaccine has a rate of adverse events similar to that of a Td vaccine (a tetanus-diphtheria vaccine containing no pertussis vaccine).[53]

References

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