Monday, February 25, 2013

Detailed Awareness Campaign On Whooping Cough (Pertusis)




Pertussis is an acute respiratory tract infection that was well described in the 1500s. Current worldwide prevalence is diminished only by active immunization. Sydenham first used the term pertussis (intense cough) in 1670; it is preferable to "whooping cough," since most infected individuals do not whoop.

ETIOLOGY.

Bordetella pertussis is the sole cause of epidemic pertussis and the usual cause of sporadic pertussis. B. parapertussis is an occasional cause of pertussis, accounting for fewer than 5% of isolates of Bordetella species in the United States. B. parapertussis contributes significantly to total cases of pertussis in other areas such as Denmark, the Czech RepublicSlovakia, and the Russian Republic. B. pertussis and B. parapertussis are exclusive pathogens of humans (and some primates). B. bronchiseptica is a common animal pathogen; occasional case reports in humans involve any body site and typically occur in immunocompromised patients or young children with unusual exposure to animals. Protracted coughing can be caused by Mycoplasma, parainfluenza or influenza viruses, enteroviruses, respiratory syncytial virus, or adenoviruses. None is an important cause of pertussis.

EPIDEMIOLOGY.

Worldwide there are 60 million cases of pertussis a year with more than half a million deaths. During the prevaccine era of 1922–1948, pertussis was the leading cause of death from communicable disease among children under 14 yr of age in the United States. Widespread use of pertussis vaccine is responsible for a dramatic decline in cases. The high incidence of disease in developing and developed countries, such as Italy and certain regions of Germany, where vaccine coverage is low, or Nova Scotia, where a less potent vaccine may have been utilized, and the dramatic resurgence of disease when immunization was halted attest to the pivotal role of vaccination. In the United States, lax implementation of policy is partially responsible for the rise in annual pertussis incidence to 1.2 cases/100,000 population from 1980 through 1989 and epidemic pertussis in many states in 1989–1990 and 1993. The more than 4,500 cases reported to the Centers for Disease Control and Prevention in 1993 is the highest incidence since 1967.

Pertussis is endemic, with superimposed epidemic cycles every 3–4 yr after accumulation of a sizable susceptible cohort. The majority of cases occur from July through October. Pertussis is extremely contagious, with attack rates as high as 100% in susceptible individuals exposed to aerosol droplets at close range. B. pertussis does not survive for prolonged periods in the environment. Chronic carriage by humans is not documented. Following intense exposure as in households, the rate of subclinical infection is as high as 50% in fully immunized and naturally immune individuals. When carefully sought, a symptomatic source case can be found for most patients.

Neither natural disease nor vaccination provide complete or lifelong immunity against reinfection or disease. Protection against typical disease begins to wane 3–5 yr after vaccination and is unmeasurable after 12 yr. Subclinical reinfection undoubtedly contributes significantly to immunity against disease ascribed to both vaccine and prior infection. Adults in the United States have inadequate antibody to B. pertussis. Despite history of disease or complete immunization, outbreaks of pertussis have occurred in the elderly, in nursing homes, in residential facilities with limited exposures, in highly immunized suburbia, and in adolescents and adults with lapsing time since immunization. Coughing adolescents and adults (usually not recognized as having pertussis) are the major reservoir for B. pertussis currently and are the usual sources for "index cases" in infants and children.

In the prevaccine era and in countries such as GermanySweden, and Italy with limited immunization, the peak incidence of pertussis is in children 1–5 yr of age; infants younger than 1 yr account for less than 15% of cases. In contrast, of the almost 5,000 cases of pertussis reported in the United States during 1993, 44% were younger than 1 yr of age, 21% were aged 1–4 yr, 11% were aged 5–9 yr, and 24% were 12 yr of age or older. For those younger than 1 yr, 79% were under 6 mo and could benefit little from immunization. Children with pertussis between 7 mo and 4 yr were underimmunized. The proportion of teenagers and adults with pertussis has risen concurrently, from less than 20% in the prevaccine era to 27% in 1992–1993. Partial control by vaccination has led to the current epidemiology of pertussis in the United States and has caused vulnerability of age groups never previously affected. Without natural reinfection with B. pertussis or repeated booster vaccinations, older children and adults are susceptible to clinical disease if exposed, and mothers provide little if any passive protection to young infants. The latter observation provides correction to an old tenet that there was little transplacental protection against pertussis.

PATHOGEN AND PATHOPHYSIOLOGY. Bordetella are tiny gram-negative coccobacilli that grow aerobically on starch blood agar or completely synthetic media with nicotinamide growth factor, amino acids for energy, and charcoal or cyclodextrin resin to absorb noxious substances. Bordetella species share a high degree of DNA homology among virulence genes, and there is controversy whether sufficient diversity exists to warrant classification as distinct species. Only B. pertussis expresses pertussis toxin (PT), the major virulence protein. Serotyping is dependent upon heat-labile K agglutinogens. Of 14 agglutinogens, 6 are specific to B. pertussis. Serotypes vary geographically and over time.

B. pertussis produces an array of biologically active substances, many of which are postulated to play a role in disease and immunity. Following aerosol acquisition, filamentous hemagglutinin (FHA), some agglutinogens (especially FIM2 and FIM3), and a 69-kD nonfimbrial surface protein called pertactin (PRN) are important for attachment to ciliated respiratory epithelial cells. Tracheal cytotoxin, adenylate cyclase, and PT appear to inhibit clearance of organisms. Tracheal cytotoxin, dermonecrotic factor, and adenylate cyclase are postulated to be predominantly responsible for the local epithelial damage that produces respiratory symptomatology and facilitates absorption of PT. PT has multiple proven biologic activities (e.g., histamine sensitivity, insulin secretion, leukocyte dysfunction), some of which may account for systemic manifestations of disease. PT causes lymphocytosis immediately in experimental animals by rerouting lymphocytes to remain in the circulating blood pool. PT appears to play a central but not a singular role in pathogenesis.
Bronchiolar plugging in neonate with pertussis pneumonia

CLINICAL MANIFESTATIONS.

Pertussis is a lengthy disease, divided into catarrhal, paroxysmal, and convalescent stages, each lasting 2 wk. Classically, following an incubation period ranging from 3 to 12 days, nondistinctive catarrhal symptoms of congestion and rhinorrhea occur, variably accompanied by low-grade fever, sneezing, lacrimation, and conjunctival suffusion. As symptoms wane, coughing begins first as a dry, intermittent, irritative hack and evolves into the inexorable paroxysms that are the hallmark of pertussis. Following the most insignificant startle from a draught, light, sound, sucking, or stretching, the well-appearing young infant begins to choke, gasp, and flail extremities, eyes watering and bulging, face reddened. Cough (expiratory grunt) may not be present, prominent, or appreciated at this stage and age. Whoop (forceful inspiratory gasp) infrequently occurs in infants under 3 mo who are exhausted or lack muscular strength to create sudden negative intrathoracic pressure. The well-appearing playful toddler with similarly insignificant provocation suddenly expresses an anxious aura and may clutch a parent or comforting adult before beginning a machine-gun burst of uninterrupted coughs, chin and chest held forward, tongue protruding maximally, eyes bulging and watering, face purple, until at the seeming last moment of consciousness, coughing ceases and a loud whoop follows as inspired air traverses the still partially closed airway. The episode may end with expulsion of a thick plug of inspissated tracheal secretions, denuded cilia, and necrotic epithelium. Adults describe a sudden feeling of strangulation followed by uninterrupted coughs, feeling of suffocation, bursting headache, diminished awareness, and then the chest heaves and air rushes into the lungs, usually without a whoop. Post-tussive emesis is common in pertussis at all ages and is a major clue to the diagnosis in adolescents and adults. Post-tussive exhaustion is universal. The number and severity of paroxysms progress over days to a week (more rapidly in young infants) and remain at that plateau for days to weeks (longer in young infants). At the peak of the paroxysmal stage, patients may have more than one episode hourly. As paroxysmal stage fades into convalescence, the number, severity, and duration of episodes diminish. Paradoxically in infants, with growth and increased strength, cough and whoops may become louder and more classic in convalescence.
   
Children during the cough paroxism

  
Children during the cough paroxism

 
Apnea

Malnutrition in pertussis patient

 
Filatov’s sign (ulcer on the tongue frenula)

Immunized children have foreshortening of all stages of pertussis. Adults have no distinct stages. In infants under 3 mo the catarrhal phase is usually a few days or not recognized at all when apnea, choking, or gasping cough herald the onset of disease; convalescence includes intermittent paroxysmal coughing throughout the 1st yr of life including "recurrences" with subsequent respiratory illnesses; these are not due to recurrent infection or reactivation of B. pertussis.

The physical examination is generally uninformative. Signs of lower respiratory tract disease are not expected. Conjunctival hemorrhages and petechiae on the upper body are common.
 
Conjunctival hemorrhages and bruises on the lower eyelids

Conjunctival hemorrhages

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS.

Pertussis should be suspected in any individual who has pure or predominant complaint of cough, especially if the following are absent: fever, malaise or myalgia, exanthem or enanthem, sore throat, hoarseness, tachypnea, wheezes, and rales. For sporadic cases, a clinical case definition of cough of 14 or more days' duration with at least one associated symptom of paroxysms, whoop, or post-tussive vomiting has sensitivity of 81% and specificity of 58% for culture confirmation. Approximately 25% of university students studied randomly in California and Australia without known contact with pertussis who had coughing illness for 7 days or more had pertussis. Apnea or cyanosis (before appreciation of cough) is a clue in infants under 3 mo. B. pertussis is an occasional cause of sudden infant death.

Adenoviral infections are usually distinguishable by associated features, such as fever, sore throat, and conjunctivitis. Mycoplasma causes protracted episodic coughing, but there is usually a history of fever, headache, and systemic symptoms at the onset of disease as well as frequent finding of rales on auscultation of the chest. Although pertussis is often included in the laboratory evaluation of young infants with "afebrile pneumonia," B. pertussis is associated uncommonly with staccato cough (breath with every cough), purulent conjunctivitis, tachypnea, rales or wheezes that typify infection due to Chlamydia trachomatis, or predominant lower respiratory tract signs that typify infection due to respiratory syncytial virus. Unless the infant with pertussis has secondary bacterial pneumonia (and is then ill appearing), the examination between paroxysms is entirely normal, including respiratory rate.

Leukocytosis (15,000–100,000 cells/mm3) due to absolute lymphocytosis is a characteristic in late catarrhal and paroxysmal stages. Lymphocytes are of T- and B-cell origin and are normal small cells, rather than the large atypical lymphocytes seen with viral infections. Adults and partially immune children have less impressive lymphocytosis. Absolute increase in neutrophils suggests a different diagnosis or secondary bacterial infection. Eosinophilia is not common in pertussis, even in young infants. A severe course and death are correlated with extreme leukocytosis (median peak white cell count fatal vs nonfatal cases, 94 vs 18 ´ 109 cells/L) and thrombocytosis (median peak platelet count fatal vs nonfatal cases, 782 vs 556 ´ 109/L). Mild hyperinsulinemia and reduced glycemic response to epinephrine have been demonstrated; hypoglycemia is only reported occasionally. The chest radiograph is mildly abnormal in the majority of hospitalized infants showing perihilar infiltrate or edema (sometimes with a butterfly appearance) and variable atelectasis. Parenchymal consolidation suggests secondary bacterial infection. Pneumothorax, pneumomediastinum, and air in soft tissues can be seen occasionally.

All current methods for confirmation of infection due to B. pertussis have limitations in sensitivity, specificity, or practicality. Isolation of B. pertussis in culture remains the gold standard and is a more sensitive and specific method of diagnosis than direct fluorescent antibody (DFA) testing of nasopharyngeal secretions if careful attention is paid to specimen collection, transport, and isolation technique. Cultures are positive during the catarrhal stage and escalating paroxysmal stage but are less likely to be positive in partially immune individuals and in those who have received amoxicillin or erythromycin. The specimen is obtained by deep nasopharyngeal aspiration or by use of a flexible swab (Dacron or calcium alginate preferred) held in the posterior nasopharynx for 15–30 sec. (or until coughing). A 1.0% casamino acid liquid is acceptable for holding a specimen up to 2 hr; Stainer-Scholte broth or Regan-Lowe semisolid transport media is used for longer periods, up to 4 days. Regan-Lowe charcoal agar with 10% horse blood and 5–40 mg/mL cephalexin or Stainer-Scholte media with cyclodextrin resins are the preferred isolation media. Cultures are incubated at 35–37ยบ F in humid environment (with or without 5% CO2) and examined daily for 7 days for slow-growing, tiny glistening colonies. DFA testing of potential isolates using specific antibody for B. pertussis and B. parapertussis maximizes recovery. Direct testing of nasopharyngeal secretions by DFA is a rapid test, especially helpful in patients who have received antibiotics, but is only reliable in laboratories with continuous experience. Experience with the polymerase chain reaction to test nasopharyngeal specimens is increasing rapidly. Serologic tests for detection of a variety of antibodies to components of the organism in acute and convalescent samples are the most sensitive tests and are useful epidemiologically. They are not generally available, are not helpful during acute illness, and are difficult to interpret in immunized individuals.

COMPLICATIONS AND PROGNOSIS. Rates of complications are difficult to establish because severe outcomes are preferentially reported, but infants under 6 mo of age have excessive mortality and morbidity. Those under 2 mo of age have the highest reported rates of pertussis-associated hospitalization (82%), pneumonia (25%), seizures (4%), encephalopathy (1%), and death (1%).

The principal complications of pertussis are apnea, secondary infections (such as otitis media and pneumonia), and physical sequelae of forceful coughing. The need for intensive care and artificial ventilation is usually limited to infants under 3 mo of age. Apnea, cyanosis, and secondary bacterial pneumonia are events precipitating intubation and ventilation. Bacterial pneumonia and/or adult respiratory distress syndrome are the usual cause of death at any age; pulmonary hemorrhage has occurred in the neonate. Fever, tachypnea or respiratory distress between paroxysms, and absolute neutrophilia are clues to pneumonia. Expected pathogens include Staphylococcus aureus, S. pneumoniae, and bacteria of mouth flora. Bronchiectasis has been reported rarely following pertussis. Abnormal pulmonary function may persist for 12 mo after uncomplicated pertussis in children under 2 yr.

Increased intrathoracic and intra-abdominal pressure during coughing can result in conjunctival and scleral hemorrhages, petechiae on the upper body, epistaxis, hemorrhage in the central nervous system and retina, pneumothorax and subcutaneous emphysema, and umbilical and inguinal hernias. Laceration of the lingual frenulum is not uncommon. Rectal prolapse, once reported as a frequent complication of pertussis, was probably due to pertussis in malnourished children or missed diagnosis of cystic fibrosis. It is distinctly unusual and should elicit evaluation for underlying condition. Especially in infants in developing countries, dehydration and malnutrition following post-tussive vomiting can have a severe impact. Tetany has been associated with profound post-tussive alkalosis.

Central nervous system abnormalities occur at a relatively high frequency and are almost always the result of hypoxemia or hemorrhage associated with coughing or apnea in young infants. Apnea or bradycardia or both may occur from apparent laryngospasm or vagal stimulation just before a coughing episode, from obstruction during an episode, or from hypoxemia following an episode. Lack of associated signs in some young infants with apnea raises the possibility of a primary effect of PT on the central nervous system. Seizures are usually the result of hypoxemia, but hyponatremia from inappropriate secretion of antidiuretic hormone during pneumonia can occur. Although hypoglycemia, a direct effect of PT, or secondary infection due to neurotropic virus have been postulated mechanisms for neurologic symptomatology, no animal data support such theories, and the only neuropathology documented in humans is parenchymal hemorrhage and ischemic necrosis.

TREATMENT.

Assessment and Supportive Care. Goals of therapy are to limit the number of paroxysms, to observe severity of cough to provide assistance when necessary, and to maximize nutrition, rest and recovery without sequelae. Infants less than 3 mo of age are admitted to hospital almost without exception, at between 3 and 6 mo unless witnessed paroxysms are not severe, and at any age if complications occur or the family is unable to provide supportive care. Prematurely born young infants and children with underlying cardiac, pulmonary, muscular, or neurologic disorders have a high risk for severe disease.

The specific, limited goals of hospitalization are to (1) assess progression of disease and likelihood of life-threatening events at peak of disease, (2) prevent or treat complications, and (3) educate parents in the natural history of the disease and in care that will be given at home. For most infants without complications, this is accomplished in 48–72 hr. Heart rate, respiratory rate, and pulse oximetry are continuously monitored, with alarm settings so that every paroxysm is witnessed by health care personnel. Detailed cough records and documentation of feeding, vomiting, and weight change provide data to assess severity. Typical paroxysms that are not life threatening have the following features: duration less than 45 sec; red but not blue color change; tachycardia, bradycardia (not <60 beats/min in infants), or oxygen desaturation that spontaneously resolves at the end of the paroxysm; whooping or strength for self-rescue at the end of the paroxysm; self-expectorated mucus plug; and post-tussive exhaustion but not unresponsiveness. Assessing the need to provide oxygen, stimulation, or suctioning requires skilled personnel who can document an infant's ability for self-rescue but who will intervene rapidly and expertly when necessary. Infants whose paroxysms repeatedly lead to life-threatening events despite passive delivery of oxygen require intubation, paralysis, and ventilation. Subsequent management is difficult, with frequent need to suction the airway and intervene when bradycardia or secondary pulmonary processes occur. Mist by tent, specifically avoided by some experts, can be useful in some infants with thick tenacious secretions and excessively irritable airways. The benefit of a quiet, dimly lighted, undisturbed, comforting environment cannot be overestimated or forfeited in a desire to monitor and intervene. Feeding children with pertussis is challenging. The risk of precipitating cough by nipple feeding does not warrant nasogastric, nasojejunal, or parenteral alimentation in most infants. The composition or thickness of formula does not affect the quality of secretions, cough, or retention. Large-volume feedings are avoided.

Within 48–72 hr, the direction and severity of disease is usually obvious by analysis of recorded information. Many infants have marked improvement following hospitalization and antibiotic therapy, especially if they are early in the course of disease or have been removed from aggravating environmental smoke, excessive stimulation, or a dry or polluted heat source. Apnea and seizures occur in the incremental phase of illness and in those with complicated disease. Portable oxygen, monitoring, or suction apparatus should not be needed at home.

Therapeutic Agents. ANTIMICROBIAL AGENTS. An antimicrobial agent is always given when pertussis is suspected or confirmed for potential clinical benefit and to limit the spread of infection. Erythromycin, 40–50 mg/kg/24 hr, orally in four divided doses (maximum 2 g/d 24 hr) for 14 days is standard treatment. Some experts prefer the estolate preparation, but ethylsuccinate and stearate are also efficacious. Small studies of erythromycin ethylsuccinate given at a dosage of 50 mg/kg/24 hr divided into two doses, at a dosage of 60 mg/kg/24 hr divided into three doses, and erythromycin estolate given at a dosage of 40 mg/kg/24 hr divided into two doses showed elimination of organisms in 98% of children. Ampicillin, rifampin, and trimethoprim-sulfamethoxazole are modestly active but 1st and 2nd generation cephalosporins are not. In clinical studies, erythromycin is superior to amoxicillin for eradication of B. pertussis and is the only agent with proven efficacy.

SALBUTAMOL. A handful of small clinical trials and reports suggest a modest reduction of symptoms from the b{beta}2-adrenergic stimulant salbutamol (albuterol). No rigorous clinical trial has demonstrated a beneficial effect; one small study showed no effect. Fussing associated with aerosol treatment triggers paroxysms.

CORTICOSTEROIDS. No randomized, blinded clinical trial of sufficient size has been performed to evaluate the usefulness of corticosteroids in the management of pertussis. Studies in animals have shown a salutary effect on disease manifestations that do not have a corollary in respiratory infection in humans. Their clinical use is not warranted.

PERTUSSIS IMMUNE GLOBULIN. Hyperimmune serum, derived from adults convalescing from pertussis, was widely prescribed and regarded as beneficial in the 1930s and 1940s; later studies and the only placebo-controlled trial demonstrated little or no value. In a recent double-blind study in Sweden using large intramuscular doses of hyperimmune serum (raised by immunization of adults), whooping (but not cough or vomiting) was significantly reduced in infants treated in the 1st wk of disease compared with patients given placebo. Use of an immunoglobulin preparation of any sort is not warranted unless further study confirms beneficial effect.

CONTROL MEASURES.

Isolation. The patient is placed in respiratory isolation for at least 5 days after initiation of erythromycin therapy.

Care of Household and Other Close Contacts. Erythromycin, 40–50 mg/kg/24 hr, orally in four divided doses (maximum 2 g/24 hr) for 14 days should be given promptly to all household contacts and other close contacts, such as those in day care, regardless of age, history of immunization, or symptomatology. Visitation and movement of coughing family members in the hospital must be assiduously controlled until erythromycin has been taken for 5 days. Close contacts younger than 7 yr who are underimmunized should be given a pertussis-containing vaccine, with further doses to complete recommended series. Children younger than 7 yr who received a 3rd dose 6 mo or more before exposure, or a 4th dose 3 yr or more before exposure, should receive a booster dose. If infection with B. pertussis is documented at any age, the individual is exempted from routine pertussis immunization. Antimicrobial prophylaxis is not routinely recommended for exposed health care workers. Coughing health care workers, with or without known exposure to pertussis, should be tested for pertussis promptly. For major hospital outbreaks, multifaceted control procedures including targeted erythromycin treatment of coughing individuals and subsequent mass erythromycin prophylaxis may contain hospital spread.

PREVENTION Universal immunization of children with pertussis vaccine, beginning in infancy, is central to the control of pertussis. Despite enormous effort, the critical mechanism(s) of immunity following disease or vaccination, a serologic correlate of protection, and the cause of vaccine-associated adverse events are not known. The only current standards for vaccine usefulness are clinical efficacy and safety. Current goals of immunization are protection of the individual from a significant coughing illness and control of endemic and epidemic disease.

Whole Cell Vaccine. The vaccine currently used for primary immunization series in the United States and recommended by the World Health Organization for use throughout most of the world is a killed whole cell vaccine composed of a suspension of inactivated B. pertussis, combined with diphtheria and tetanus (DT) toxoids and aluminum-containing adjuvants (DTP vaccine). Potency of pertussis vaccine is assayed in the mouse by intracerebral challenge–protection test, a standard shown to correlate with protective efficacy of vaccine in humans. Vaccine potency is translated to opacity units (also a safety standard) or protective units. U.S. preparations contain 4–12 protective units and not more than 16 opacity units per 0.5-mL dose. Efficacy of whole cell vaccine varies by case definition from 64% for mild cough, to 81% for paroxysmal cough, and to 95% for severe clinical illness. Composition of the preparation used, degree of match between agglutinogen types in vaccine and challenge strain, type of exposure, time after immunization, and requirement for culture confirmation of cases all impact on estimates of vaccine efficacy. Individuals over 7 yr of age are not routinely given pertussis-containing vaccine. When used in adults to control a hospital outbreak, whole cell vaccine was found to be less reactogenic than reported in children.

A major limitation of whole cell vaccine use has been the associated reactogenicity, reported a decade ago to occur in approximately 75% of vaccinees. Compared to DT, DTP vaccine has significantly more local reactions, such as pain, swelling, erythema, and systemic reactions, such as fever, fretfulness, crying, drowsiness, and vomiting. These manifestations occur within several hours of immunization and subside spontaneously without sequelae. Recent studies report lower rates of common local and systemic reactions, suggesting that modifications of whole cell vaccine have occurred. Severe anaphylaxis or sterile abscess are extremely rare following DTP vaccine. Transient urticaria is uncommon, is probably related to circulating antigen antibody complex, and unless it occurs within minutes of immunization is unlikely to be IgE mediated, serious, or recur on subsequent immunization.

Seizures, occurring within 48 hr of approximately 1:1,750 doses administered, are brief, generalized, and self-limited, occurring in febrile children in almost all instances. They occur more commonly in those with a personal or family history of convulsion and do not result in epilepsy or permanent neurologic sequelae. Persistent inconsolable crying or screaming for 3 or more hours reported after 1% of doses administered, usually in very young infants who have local reactions, is not unique to pertussis immunization and appears to be a manifestation of pain in many instances. Collapse or shocklike state (hypotonic-hyporesponsive episode), usually unrelated to fever or local reactions, has been observed after approximately 1:1,750 pertussis vaccinations, usually in young infants. It appears to be uniquely associated with pertussis vaccine and has no permanent neurologic sequelae. Sixty children were carefully evaluated immediately following serious pertussis vaccine-related adverse events, including seizure, persistent inconsolable crying, extremely high fever, and hypotonic-hyporesponsive episode. Ninety per cent of seizures were typical febrile seizures. No metabolic derangement or measurable pertussis toxin was found in the blood. Infants under 1 yr of age tended to have higher than expected insulin values, suggesting a possible individual age-related susceptibility or vaccine-induced alteration in insulin regulation.

Very rarely (1:140,000 doses administered) pertussis vaccine may be associated with acute neurologic illness in children who were previously normal. Severe adverse events, such as death, encephalopathy, onset of a seizure disorder, developmental delay, or learning or behavioral problems, have occurred in individuals temporally associated with pertussis immunization or alleged to be causally associated. Five major epidemiologic studies have examined neurologic risks related to pertussis immunization. Sudden infant death (SIDS) and infantile spasm were found to be neither temporally nor causally related. Analysis and reanalysis by seven major committees found information insufficient to accept a causal relationship between DTP and chronic neurologic disorders. Consideration of benefits versus risks of whole cell vaccine has repeatedly concluded in favor of its continued use.

Acellular Vaccine. Purified component acellular pertussis (aP) vaccines, originally developed in Japan, are immunogenic and associated with fewer adverse events when compared with DTP. Vaccines provided by six manufacturers have been used exclusively in Japan since 1981, and their use has controlled pertussis. A randomized, placebo-controlled (but not DTP-controlled) efficacy trial of two acellular pertussis vaccines (developed by the Japanese Institute of Health and conducted in Sweden during 1986 and 1987 under sponsorship of the United States) showed slighter lower efficacy of these acellular vaccines compared historically with whole-cell pertussis vaccine used in the United States. Lower reactogenicity of acellular vaccines and good immunogenicity in American toddlers, coupled with evidence of efficacy in household-exposure and population-based studies from Japan, led to U.S. licensure (1991 and 1992) of DTaP for use in children 15 mo of age or older as the 4th and/or 5th doses of the recommended DTP series. These vaccines have been well tolerated, and use is associated with fewer common local reactions and systemic symptoms, fever, and febrile seizures. Whether rare, more serious adverse events associated with DTP will occur less frequently after DTaP is not known.

Immunogenicity and low reactogenicity of 13 candidate acellular vaccines, multinationally manufactured, and containing variably PT, FHA, PRN, FIM2, FIM3 have been documented. Efficacy trials for primary immunization are ongoing in several countries. Experience is accumulating with use of acellular vaccines in adults as well. Licensure of one or more DTaPs in the United States for primary immunization awaits results of these trials. In countries where pertussis has been partially controlled, further reduction of cases will require implementation of booster doses of pertussis vaccine throughout life.


References:
Main:
1.     Current therapy in pediatric infectious diseases – 2 edited by John D. Nelson, M. D. – B.C. Decker  inc. Toronto, Philadelphia, 1988, - P. 134-138, 285.
2.     Ambulatory pediatric care (edited by Robert A. Derchewitz; - 2 nd ed. – Lippincot – Raven, 1992. – P. 570-574; 255.          
3.     Principles and Practice of Pediatric Infectious Diseases. / Edited by Saran S. Long, Larry K. Pickering, Charles G. Prober, PhiladelphiaPa: Churchill Livingstone; 1997. – 1921 p.

Additional:
1.     Textbook of Pediatric Nursing.  Dorothy R. Marlow; R. N., Ed. D. –London, 1989.-661p.
2.     Pediatrics ( 2nd edition, editor – Paul H.Dworkin, M.D.) – 1992. – 550 pp.

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