Whooping cough (pertussis) is a common acute respiratory infectious disease in children, caused by the Bordetella pertussis bacterium. It is characterized by paroxysmal spasmodic coughing, often ending with a distinctive inspiratory whooping sound. The illness can last for weeks or even up to three months, hence the name "whooping cough." Infants with this disease are prone to complications such as asphyxia, pneumonia, and encephalopathy, with a high mortality rate. In recent years, there has been an increasing trend of cases among infants and adults.

bubble_chart Epidemiology

Whooping cough is a global disease, with over 60 million cases reported worldwide annually and approximately 1 million deaths attributed to it. This Bingchuan is highly contagious, comparable to measles and chickenpox, with over 90% of susceptible children in close contact becoming infected. It can occur year-round, though it is more common in winter and spring. However, epidemic peaks in June, July, and August are not uncommon. Cases are mostly sporadic but can also become epidemic, particularly in collective childcare settings.

Patients (including atypical cases) are the primary source of pestilence. Transmission mainly occurs through respiratory droplets. Asymptomatic carriers can also spread the disease. Since the bacterium has weak survival ability outside the body, indirect pestilence through other objects is unlikely. The pestilence is most potent from the late incubation period to within 6 weeks of onset (especially during the 2–3 week catarrhal stage).

People of all ages can contract the disease, but it predominantly affects infants and young children. About two-thirds of cases occur in children under 7 years old. Newborns have minimal specific antibodies inherited from their mothers, so cases among them are not rare. Among whooping cough fatalities, 40% are infants under 5 months old. Approximately 10% of whooping cough cases and 70% of deaths occur in infants under 1 year old. Among the 742 cases observed in our hospital over the past 4 years, the majority were aged 1–5 years (especially 1–2 years). In recent years, there has been an increasing trend in cases among adolescents and adults.

The whooping cough bacillus (Bordetella pertussis) is the pathogenic bacterium of whooping cough, a Gram-negative short coccobacillus. It generally requires a large amount (15-25%) of fresh blood in the culture medium to grow well, with the blood-glycerol-potato (B-G medium) being the most suitable for isolating this bacterium. Freshly isolated whooping cough bacilli are Phase I bacteria. Phase I bacteria have smooth colonies, possess a capsule, are highly virulent, and contain internal toxins and exotoxins. After continuous subculturing, the colonies become rough, and their virulence gradually weakens, with varying antigenic strength. These non-pathogenic whooping cough bacilli are referred to as Phase II, III, and IV. Only Phase I whooping cough bacteria cause disease and produce symptoms, and vaccines must also be made from Phase I bacteria to induce immunity. This bacterium has weak survival ability outside the human body, surviving only 2 hours at room temperature, being inactivated after 1 hour of sunlight exposure or heating at 60°C for 15 minutes, and can also be quickly eliminated by common chemical disinfectants. Within the Bordetella genus, there are also the parapertussis bacillus (B. parapertussis) and the bronchiseptic bacillus (B. bronchiseptica). These two are morphologically similar to the whooping cough bacillus. The former can cause respiratory symptoms similar to whooping cough but does not share cross-immunity with the whooping cough bacillus. The latter is primarily a pathogen for animals. The fourth species in the Bordetella genus is B. avium, a bacterium similar to the bronchiseptic bacillus, which is a pathogen for birds and has not been known to cause infections in humans.

After entering the human body, the bacteria adhere to the epithelial cells of the respiratory tract and multiply there, producing toxins. Upon adhesion, they inhibit the normal ciliary movement of the epithelial cells, and the bacterial toxins can also paralyze the cilia and cause cell necrosis. The bronchial mucous membrane becomes extensively inflamed, with increased mucus secretion and ciliary damage, impairing mucus clearance. The persistent stimulation of the sensory nerve endings in the bronchial mucous membrane by the mucus reflexively triggers intense, continuous coughing. Some also believe that the spasmodic cough is caused by the cough center's hypersensitivity to the bacteria. The bacteria can produce various cellular products, such as histamine sensitization factor (HSF), which increases the body's sensitivity to environmental and generation and transformation stimuli; lymphocytosis promoting factor (LPF), which elevates lymphocyte counts; and islets-activating protein (IAP), which boosts insulin secretion and may lead to clinical hypoglycemia symptoms. These substances are related to the exotoxins produced by the whooping cough bacillus and can cause cell necrosis and systemic symptoms.

After adhering to and multiplying on the epithelial cells, the bacteria can induce necrosis in the middle and basal layers of the bronchial epithelium, accompanied by neutrophil infiltration and the typical pathological changes of whooping cough. Autopsies often reveal peribronchial infiltration and interstitial pneumonia. Due to mucus plugs causing complete or partial obstruction of small bronchi, localized atelectasis and lung qi swelling may occur. Bronchopneumonia is usually caused by secondary bacterial infections. The brain may exhibit congestion and petechial hemorrhages, particularly in cases with convulsions. Extensive hemorrhage in the brain parenchyma or subarachnoid space is rare, but cerebral edema and neuronal degeneration may occur.

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The incubation period is generally 7 to 10 days, but can extend up to 21 days. The clinical course can be divided into the late stage [third stage].

(1) Catarrhal Stage: From the onset of the disease until the appearance of whooping cough, it generally lasts about 1 to 2 weeks. The initial symptoms resemble a common cold, including cough, runny nose, sneezing, and grade I fever, or there may only be a dry cough, which often goes unnoticed. As other symptoms gradually disappear, the cough worsens, being milder during the day and more severe at night, eventually developing into a whooping cough.

(2) Paroxysmal Stage: This stage typically lasts 2 to 6 weeks (ranging from a few days to over 2 months). The hallmark of this stage is paroxysmal, spasmodic coughing. During an episode, the patient experiences a series of rapid, uninterrupted short coughs (10 to dozens) in an expiratory state, followed by a deep, prolonged inhalation. Because the larynx remains in a spasmodic state, this is accompanied by a high-pitched, crowing sound. This cycle repeats multiple times until thick mucus is expelled. Severe coughing may lead to incontinence of urine, clenched fists, flexed elbows, wide-eyed expressions, flushed face, tears, a forward-leaning head, open mouth with protruding tongue, and cyanosis of the lips, all indicating extreme distress. The episode usually ends after vomiting. Mild cases may experience several episodes a day, while severe cases can have dozens, mostly at night. Triggers include running, eating, exposure to cold, smoke, or crying. There are usually no obvious warning signs before an episode, and the intervals between episodes are unremarkable. During coughing, increased pressure in the superior vena cava impedes venous return to the heart, leading to static blood, often manifesting as facial and eyelid edema. Intense paroxysmal coughing may cause epistaxis, hemoptysis, or subconjunctival hemorrhage, and even intracranial hemorrhage. Frequent coughing can disrupt sleep, leaving the child fatigued, inactive, and with reduced appetite, compounded by vomiting and secondary infections, leading to nutritional deficiencies. If no secondary infection occurs, the child usually has a normal temperature, with no positive signs in the lungs or occasional non-specific rales.

Newborns and young infants often do not exhibit typical whooping cough but may show paroxysmal breath-holding and cyanosis, which can easily lead to asphyxia or convulsions. Breathing may stop during the expiratory phase, with the heart rate initially increasing, then slowing or even stopping. Without timely artificial respiration, oxygen, or other emergency measures, asphyxial death may occur.

Adult Whooping Cough: In recent years, cases of whooping cough among adolescents and adults have been increasing, accounting for up to 10.2% of total cases during outbreaks. In one group of culture-confirmed adult whooping cough cases, the average age was 35. Symptoms included typical whooping cough and post-paroxysmal vomiting, but some only had a dry cough lasting several weeks, with rare complications. Most adults can continue working, and while they may not experience significant distress, they can serve as sources of pestilence, especially posing a threat to children, which warrants attention.

(3) Convalescent Stage: Lasts about 2 to 3 weeks. Paroxysmal whooping cough lessens in severity and frequency, and the crowing sound disappears. The child's energy and appetite gradually return to normal. If complications arise, this stage may be prolonged.

bubble_chart Auxiliary Examination

(1) White Blood Cell Count By the end of the first week of illness and during the early stage of paroxysmal cough, the white blood cell count is often elevated, generally ranging from 20,000 to 30,000/mm³ or higher, with lymphocytes accounting for 60–80%. If secondary infection occurs, the lymphocyte count decreases relatively.

(2) Cell Culture In the early stage of illness, nasopharyngeal swabs are collected, and during the paroxysmal cough stage, specimens are collected using the cough plate method. Bacterial culture is performed using B-G medium, with a higher positive rate in the early stages. The positive rate can reach 90% in the initial catarrhal stage, but it generally falls below 50% during the paroxysmal cough stage. After 2–3 weeks of paroxysmal cough, cultures are almost entirely negative. Detecting *whooping cough* bacillus colonies on the culture medium using the direct fluorescent antibody staining method is a reliable approach.

(3) Fluorescent Antibody Staining This method involves examining nasopharyngeal swab smears and offers the advantage of rapid diagnosis. However, its specificity is poor, and it is only used as an auxiliary to culture.

(4) Serological Tests Paired serum agglutination tests and complement fixation tests are performed. A rising antibody titer can confirm the diagnosis. Recently, enzyme-linked immunosorbent assays (ELISA) have been used to measure IgM, IgG, and IgA antibodies, aiding in early diagnosis. Some also use a single serum agglutination antibody titer of 1:320 during the *stage of convalescence* as a positive diagnostic value.

Other methods for detecting *whooping cough* bacillus or its components, such as dot blot hybridization, PCR, morphological analysis in tissue cell culture, and enzyme activity assays, are still in the laboratory or clinical observation stage and have not yet been widely applied.

bubble_chart Diagnosis

Based on exposure history and typical manifestations during the paroxysmal stage, a clinical diagnosis can be made even in the absence of typical paroxysmal cough by combining characteristic blood test changes. Etiological diagnosis relies on bacterial culture and specific serological tests. For persistent cough of unknown cause in all age groups, especially those with paroxysmal symptoms, the possibility of this disease should be considered, and further testing is necessary.

bubble_chart Treatment Measures

(1) General Therapy Implement respiratory isolation, maintain fresh air, and avoid all factors that may induce spasmodic cough. Provide good nursing care to prevent complications. Pay attention to nutrition.

(2) Antibiotic Therapy Administer during the catarrhal stage or early spasmodic stage to reduce infectivity, alleviate symptoms, and shorten the course of the disease.

1. Erythromycin 40–50 mg/kg per day, with a maximum dose of 2 g/day, divided into 3–4 oral doses, for 7–14 days. TMP (trimethoprim) may also be added at 6 mg/kg per day, divided into two oral doses, for a course of 7 days.

2. Ampicillin 100–150 mg/kg per day, intramuscular injection, for a course of 7–10 days. Some suggest that a high dose of 1–2 g per dose, administered intramuscularly twice daily for 7 days, may be effective.

3. Kanamycin, compound SMZ (sulfamethoxazole-trimethoprim), and isoniazid may also be used, each for a course of 7–10 days.

(3) Symptomatic Treatment Expectorants and antitussives such as ammonium chloride may be used. Salbutamol (albuterol) 0.5 mg/kg can alleviate cough symptoms. Chlorpromazine and similar drugs may reduce nocturnal coughing and improve sleep. For infants with apnea, perform artificial respiration immediately, administer oxygen, and provide antispasmodic and expectorant treatment if necessary. Procaine may be administered intravenously, 1–2 times daily for 3–5 days, to reduce apnea or convulsions, while monitoring heart rate and blood pressure. Dehydrating agents may be used for whooping cough encephalopathy. Address hypocalcemia, hypoglycemia, etc., with appropriate symptomatic treatment.

(4) Treatment of Complications Provide corresponding treatment based on the specific complication.

(5) Corticosteroids Use only for short-term treatment in critically ill patients, such as infants or those with encephalopathy. Prednisolone 15–20 mg/day, orally. Alternatively, administer hydrocortisone intravenously. Monitor for corticosteroid side effects.

bubble_chart Prognosis

It is related to the patient's age, general health condition, and the presence of complications. In recent years, due to the ability to provide early treatment, the mortality rate has significantly decreased. However, newborns and young infants are prone to complications such as pneumonia and encephalopathy, and the prognosis remains critical. Children with rickets who contract whooping cough often experience more severe conditions.

bubble_chart Prevention

(1) Isolation of the source of pestilence Strict implementation of respiratory isolation for patients with this disease is a crucial preventive measure. The isolation period begins at the onset of symptoms and lasts for 7 weeks, or 4 weeks from the start of whooping cough. Susceptible children in close contact (especially in collective settings) require quarantine for 3 weeks. Adult patients should avoid contact with children. The epidemic area only needs ventilation and air exchange.

(2) Protection of susceptible individuals

1. Active immunization Currently, the commonly used DPT (diphtheria toxoid, whooping cough vaccine, tetanus toxoid) triple vaccine is administered as primary immunization to infants aged 3–6 months via subcutaneous injection in three doses. During an epidemic, infants as young as 1 month can receive vaccination. Full-course immunization is emphasized, followed by booster doses as required. The whooping cough vaccine may occasionally cause neurological reactions such as encephalopathy. Therefore, it should not be administered to individuals with pre-existing brain disorders or convulsive diseases, or those who experienced convulsions after the first dose of the whooping cough vaccine. Vaccination with the whooping cough vaccine is also suspended during the Japanese encephalitis epidemic season. Although the current whole-cell whooping cough vaccine has played a role, its efficacy is still suboptimal, with reports of children and adults contracting whooping cough post-immunization.

Acellular whooping cough vaccine: This vaccine uses certain components of the Bordetella pertussis bacterium rather than the whole cell. It offers better protection than the whole-cell vaccine while avoiding its adverse reactions. In 1981, Japan's Sato successfully developed an acellular whooping cough vaccine primarily composed of pertussis toxin (PT) and filamentous hemagglutinin (FHA). Subsequently, countries such as the UK, the US, and Sweden developed various acellular whooping cough component vaccines, achieving effective results in populations. It has been confirmed that, regardless of the acellular whooping cough component vaccine, pertussis toxin (PT) antigen is an essential component. Further research has revealed that pertussis toxin monoclonal antibodies (PT-McAb) can specifically neutralize multiple biological activities of pertussis toxin both in vitro and in vivo, while also providing protective effects against Bordetella pertussis infection.

2. Passive immunization For young infants or individuals with weak constitutions, high-titer whooping cough immunoglobulin may be administered after exposure to the patient. However, its effectiveness in preventing or alleviating symptoms is limited, so it is rarely used.

(3) Drug prophylaxis For infants exposed to the disease, erythromycin at 50 mg/kg per day, divided into four oral doses for 10–14 days, is highly effective.

bubble_chart Complications

It is more common in children and rare in adults with a philtrum.

(1) Respiratory complications: Bronchopneumonia is a common complication in infants and young children, often occurring during the paroxysmal stage. The pulmonary lesions caused by whooping cough bacillus are mainly interstitial pneumonia, but are often induced by secondary bacterial infections. Aspiration pneumonia may also occur during paroxysmal coughing. At this stage, body temperature may rise, and the paroxysmal cough may become atypical, but dyspnea, cyanosis, and prominent moist rales in the lungs are notable. If the bronchi are obstructed by mucus, it may lead to lung qi swelling; complete obstruction can cause atelectasis; if alveoli rupture, it may result in pneumothorax, mediastinal emphysema, or subcutaneous lowering qi swelling; if the bronchial membrane and pulmonary interstitium are damaged, it may lead to bronchiectasis in the future.

(2) Neurological complications: Manifested as whooping cough encephalopathy, caused by cerebral hypoxia, congestion, intracranial hemorrhage, injury to brain cells, and bacterial toxins, and is more common in young children. Symptoms include consciousness disorders, convulsions, etc. Cerebrospinal fluid usually shows no significant changes.

(3) Worsening of subcutaneous node disease: This disease can exacerbate pre-existing pulmonary subcutaneous nodes and even lead to hematogenous dissemination, resulting in foxtail millet-like subcutaneous nodes or subcutaneous node-related brain membrane inflammation.

(4) Others: Friction between the lingual frenulum and lower incisors may cause lingual frenulum ulcers. Due to increased intra-abdominal pressure during severe coughing, conditions such as umbilical hernia, inguinal hernia, and rectal prolapse may occur.

bubble_chart Differentiation

The following diseases should be differentiated from whooping cough.

(1) Acute bronchitis and pneumonia: Bronchitis caused by Haemophilus influenzae type B, adenovirus, respiratory syncytial virus, parainfluenza virus, etc., presents with severe cough, often with paroxysmal coughing. However, the severe cough appears within a few days of onset, there is no whooping sound after the paroxysmal cough, nighttime exacerbation is not necessarily present, systemic infectious toxic symptoms such as wheezing, cough, and shortness of breath are more severe during the acute phase, and fixed dry or moist rales are often heard in the lungs. The white blood cell count is normal or slightly elevated. With appropriate treatment, symptoms alleviate or disappear within a short period.

(2) Bronchial lymph node subcutaneous node: Enlarged lymph nodes compressing the bronchi or eroding the bronchial wall can cause spasmodic cough, but without the whooping sound. Diagnosis can be made based on the toxic symptoms of subcutaneous node disease, subcutaneous node bacillus test, and chest X-ray findings.

(3) Tracheobronchial foreign body: Paroxysmal spasmodic cough may occur suddenly, with a history of foreign body aspiration. The white blood cell count is not elevated, and segmental atelectasis may be seen on X-ray. Bronchoscopy can identify the foreign body.

(4) Whooping cough syndrome: Even in populations with widespread whooping cough immunization, sporadic cases of "whooping cough" may still occur. Often, adenovirus, other respiratory viruses, Mycoplasma pneumoniae, or parapertussis bacilli are isolated, but not Bordetella pertussis. The clinical symptoms, chest X-ray findings, and blood test results resemble those of typical whooping cough, and differentiation relies on etiological testing. It is estimated that about 20% of cases are caused by the aforementioned pathogens. Chlamydia infection may present with a whooping cough-like cough but without the whooping sound. Cases caused by parapertussis bacillus have milder symptoms and a shorter course.