Recent developments in pertussis

Pertussis causes nearly 300,000 deaths in children every year. Most deaths take place in developing countries, but the infection remains a priority everywhere. Pertussis vaccination protects infants and children against death and admission to hospital, but breakthrough disease in vaccinated people can happen. In high-mortality countries, the challenge is to improve timeliness and coverage of childhood vaccination and surveillance. In regions with low mortality and highest coverage, pertussis is frequently the least well-controlled disease in childhood vaccination programmes. Some countries have reported a rise in pertussis in adolescents, adults, and pre-vaccination infants, but how much these changes are real or a result of improved recognition and surveillance remains uncertain. In response, several countries have introduced adolescent and adult acellular pertussis vaccine boosters. The effect so far is unknown; assessment is impeded by poor data. Uncertainties still persist about key variables needed to model and design vaccination programmes, such as risk of transmission from adults and adolescents to infants. New vaccination strategies under investigation include vaccination of neonates, family members, and pregnant women.     

Progress in the diagnosis,prevention, and treatment of pertussis

Pertussis (“whooping cough”), caused by the gramnegative pleomorphic bacillus Bordetella pertussis, is a highly contagious, potentially life-threatening respiratory tract illness that has re-emerged worldwide as a cause of substantial morbidity and mortality in infants, children, and adolescents, even in countries with high vaccination rates. Waning immunity after immunization during childhood has been associated with a growing pool of susceptible adolescents and adults who are capable of transmitting pertussis to vulnerable unvaccinated or incompletely vaccinated infants. The use of acellular pertussis vaccine boosters in adolescents has been proposed and is likely to be recommended. Active immunization and improved methods for early diagnosis are key in the management of pertussis, and represent the most rapidly evolving aspects of this disease.     

Pertussis – eine impfpräventable Erkrankung

Pertussis (whooping cough) is caused by Bordetella pertussis and B. parapertussis. It is a purely respiratory infection, which can be highly contagious. In countries with vaccination programs, the main targets are young infants, older non-vaccinated children, adolescents and adults. The disease remains endemic and cyclical worldwide, even in countries with a sustained high vaccination coverage. Pertussis is a notifiable disease in Germany but epidemiological data might not reflect the true burden of the disease. The main symptom is coughing for prolonged periods, which can be paroxysmal. The disease can take a severe course in infants with a possible fatal outcome but adults can also have a high rate of complications. Pertussis can be diagnosed by detecting Bordetella DNA by PCR or by detection of IgG antibodies to pertussis toxin. Antibiotics, such as macrolides can stop transmission but might not relieve the symptoms. Infant vaccination, which in Germany is carried out with four doses of combination vaccines with acellular pertussis components, can prevent the majority of cases. As immunity after infection and vaccination is not permanent, additional strategies comprising school entry boosters and the vaccination of adolescents and adults, as well as vaccinating special risk groups, such as pregnant women are recommended.     

Tos ferina en España. Situación epidemiológica y estrategias de prevención y control. Recomendaciones del Grupo de Trabajo de Tos ferina

A large increase of pertussis incidence has been observed in recent years in countries with high vaccination coverage. Outbreaks of pertussis are increasingly being reported. The age presentation has a bipolar distribution: infants younger 6 months that have not initiated or completed a vaccination schedule, and adolescents and adults, due to the lost of natural or vaccine immunity over time. These epidemiological changes justify the need to adopt new vaccination strategies in order to protect young infants and to reduce pertussis incidence in all age groups.     

Rationale for pertussis booster vaccination throughout life in Europe

Although the introduction of universal pertussis immunisation in infants has greatly reduced the number of reported cases in infants and young children, disease incidence has been increasing in adolescents and adults in recent years. This changing epidemiological pattern is probably largely attributable to waning immunity after natural infection or vaccination. Furthermore, improved diagnostic testing, active surveillance, changes in disease susceptibility, vaccine characteristics, and increased awareness of the disease might also be contributing factors. Susceptibility to pertussis in adolescents and adults results not only in direct morbidity in these age groups, but also poses a transmission risk to susceptible non-immune infants who are often too young to be vaccinated. Because vaccination schedules vary across Europe, we review the pertussis situation in this region and propose considerations for use of pertussis booster vaccinations at different ages to reduce individual morbidity and transmission from present rates and increase herd protection.     

La coqueluche en pratique en 2006

Universal vaccination of infants against pertussis has transformed the epidemiology of the disease. Pertussis has however become frequent, although not often diagnosed, in adolescents and adults and thus contributes to permanent transmission of Bordetella pertussis in France and contamination of young infants at risk of severe disease. Control of transmission of pertussis in France necessitates reinforcement of vaccination with late boosters in adolescents and adults and, in addition, education of physicians to recognize and treat early cases of pertussis, especially in adolescents and adults with a persistant or chronic cough, and to take appropriate prophylactic measures (antibiotics and recall vaccination) of those in contact with confirmed cases. Effective treatment does little to reduce symptoms but it does reduce transmission. Macrolides are the recommended treatment for pertussis.     

Pertussis-induced cough

Pertussis (whooping cough) is one of the commonest vaccine preventable diseases in the UK, despite vaccination coverage being maintained for the last 15 years at over 90% among infants and the addition of a pre-school booster to the UK national immunisation programme in 2001. However, it is known that pertussis vaccine does not confer long-term immunity to clinical infection. Evidence of pertussis infection has been reported in 37% of children presenting in UK primary care and 20% of adolescents and adults presenting in Canadian health centres with persistent cough. In children and adults with persistent cough, paroxysmal coughing is the most sensitive indicator of pertussis, but has poor specificity and limited diagnostic value. Vomiting and whooping, particularly in combination, are stronger predictors of pertussis. Cough duration is longer in children than in adults with pertussis (median cough duration 112 days versus 42 days); individuals may take even longer to recover fully and regain previous levels of exercise tolerance. A diagnosis of pertussis may be confirmed by culture, Polymerase Chain Reaction (PCR) or serology. Single estimates of anti-pertussis toxin (PT) antibody titres in blood or oral fluid samples are highly specific. There are currently no proven efficacious treatments for pertussis-induced cough. Treatment with macrolide antibiotics reduces the duration of an individual's infectious period, but does not alter the duration of cough. Further research is needed to re-examine the epidemiology of pertussis in countries with different vaccination schedules, find efficacious treatments and develop methods of measuring cough frequency and severity in patients with pertussis-induced cough.     

Conduite à tenir devant un ou plusieurs cas de coqueluche

The evolution of the epidemiology of pertussis, new licensed macrolides and vaccines, new recommendations for vaccination among adolescents and adults need an update of the French guidelines for prevention of the disease around one or grouped cases of the disease. A particular attention should be raised to the diagnosis of whooping cough in adults who are presently the main reservoir of Bordetella pertussis. Whooping cough in adults presents as an unexplained prolonged cough with nocturnal exacerbation witch accounts for most of the contaminations of young infants. A bacteriological confirmation of pertussis should be provided before implementation of preventive measures: culture and PCR are presently the gold standard for the diagnosis of pertussis in infants, children and even adults who have been coughing for less than 20 days. Later on, serology (Elisa, immuno-empreinte) is the only technique available, but cannot be interpreted if the patient has been vaccinated less than one year ago. Infants under three months should be admitted to hospital and every case submitted to respiratory isolation. Eviction from the community should be pronounced within the five first days following the onset of an effective antibiotic treatment. New macrolides should be favoured: clarithromycine for seven days or azithromycine for five days. Household contacts should be given the same prophylactic antibiotic treatment: children and adolescent not correctly immunized, parents of the index case as adults parents of not or not completely immunized infants. The vaccination program of the household should be updated. The same measures should be applied in case of grouped cases (at least two contemporary or consecutive cases in the same area). In that case, the Public Health System doctors should be involved in the investigation and the classification of the cases. The close contacts not or not completely immunized should be prescribed and antibiotic prophylaxis and an update of their vaccination program. Among the occasional contacts, high-risk people only should be treated. In the day care centres an antibioprophylaxis should be given to children who have received less than four vaccine shots against pertussis and to the personnel contact to the cases as well. In the schools, the antibiotic prophylaxis should be prescribed to all children of the classroom(s) not completely vaccinated and to the teacher(s) as well. In the boarding schools and institutions with handicapped children, antibiotic prophylaxis could be applied to every member if the pertussis vaccine coverage is at less than 50%. In hospitals, coughing personnel should wear masks and investigations towards pertussis should be performed in people with a more than seven day unexplained cough. Preventive measures should be applied in case of confirmation of pertussis.     

The seroepidemiology of Immunoglobulin G antibodies against pertussis toxin in China: a cross sectional study

ABSTRACT: BACKGROUND: Pertussis is a reported vaccine-preventable respiratory disease in China. Because the routine laboratory methods for diagnosis are not in use, the reported cases are mainly in infants with classical paroxysmal cough and the true incidence related to pertussis is most likely under estimated. In China, however, few studies have attempted to address this issue. The purpose of this cross sectional study was to estimate the incidence rates using the method of sero-epidemiology of immunoglobulin (Ig) G antibodies against pertussis toxin (PT) among healthy populations in China. METHODS: Blood samples were obtained from 1313 healthy individuals aged 0 to 95 years in Guangdong province of China throughout September 2010. Serum IgG antibodies against PT were determined by commercial ELISA kits. Subjects with concentration of anti-PT IgG higher than 30 IU/mL were indicated to have recent Bordetella pertussis infection, if they have not received a booster dose of pertussis vaccine within one year. RESULTS: Of the 1313 study subjects, 117 (8.91%) were found to have anti-PT antibodies higher than 30 IU/mL. The estimated incidence of recent infection was thus 9395 per 100,000 for individuals older than 7 years. Peaks of the estimated incidence rate of recent infection were found to be 11561 per 100,000 in age group of 41 to 50 years and 11428 per 100,000 in the group aged 13 to 19 years. CONCLUSIONS: Our study indicated that B.pertussis infections are considerablely common, particularly in adolescents and adults in China. The study also stresses the importance of laboratory diagnosis for pertussis and employment of booster dose of pertussis vaccine in adolescents and adults in this country.     

Clinical definitions of pertussis: Summary of a Global Pertussis Initiative roundtable meeting, February 2011

Existing clinical case definitions of pertussis are decades old and based largely on clinical presentation in infants and children, yet an increasing burden is borne by adolescents and adults who may manifest distinct signs/symptoms. Therefore, a "one-size-fits-all" clinical case definition is no longer appropriate. Seeking to improve pertussis diagnosis, the Global Pertussis Initiative (GPI) developed an algorithm that delineates the signs/symptoms of pertussis most common to 3 age groups: 0-3 months, 4 months to 9 years, and ≥10 years. These case definitions are based on clinical presentation alone, but do include recommendations on laboratory diagnostics. Until pertussis can be accurately diagnosed, its burden will remain underestimated, making the introduction of epidemiologically appropriate preventive strategies difficult. The proposed definitions are intended to be widely applicable and to encourage the expanded use of laboratory diagnostics. Determination of their utility and their sensitivity and/or specificity versus existing case definitions is required.     

Adults are whooping, but are internists listening?

Although studies have shown that pertussis is responsible for approximately 20% to 30% of cases of cough lasting more than 2 weeks in adults and adolescents, physicians have generally considered pertussis a disease that affects only children. Epidemiologic trends demonstrate that the incidence of pertussis has been rising, especially in adolescents and adults. Consequently, pertussis is not a "zebra" diagnosis but deserves a place among the community-acquired list of adult pathogens. Increased awareness among physicians about pertussis is important because adults may transmit the infection to infants, in whom the disease often leads to hospitalization and may result in death. Reporting this disease to the local health department is critical to its control because both case-patients and their close contacts should receive antimicrobial prophylaxis. A booster vaccine for adolescents and adults is likely to become available in the near future, so this is an important time to ensure that all physicians, not just pediatricians, are knowledgeable about the diagnosis, treatment, and reporting requirements for pertussis.     

The case for maternal vaccination against pertussis

Despite high vaccine coverage, the incidence of pertussis is increasing in a number of countries. Particularly alarming is the increase of pertussis in infants too young to be (fully) vaccinated, because the highest morbidity and mortality is observed in this category. Maternal vaccination offers the possibility to protect infants from birth until immunity is induced by active vaccination, and has been shown to be effective and safe for tetanus over long periods of time. Maternal vaccination studies with whole-cell pertussis vaccines have not shown serious adverse effects in mother and child. In one study, protection of newborn babies was found. Additional support for the efficacy of maternal vaccination comes from studies showing that transfer of antibodies confers protection against pertussis. Maternal vaccination might be an effective way to decrease morbidity and mortality caused by pertussis in newborn babies.     

Whooping cough: the current scene

Pertussis, a highly contagious disease caused by Bordetella pertussis, is making a comeback globally despite good immunization coverage. The developed countries have also shown a shift in the epidemiology of the disease to the adolescent and the adult age group, leading to a revision of their vaccination policies. The disease epidemiology in the South East Asian region seems poised for a similar change. Outbreaks have been reported among children and adults in countries such as Afghanistan, Israel, and Taipei. The anticipation and early recognition of this change in the epidemiology is important because the affected adolescents and adults act as reservoirs of the disease to the vulnerable population of infants, for whom the disease can be life threatening. The clinical presentation can be atypical in the adolescent age group, and the disease is often misdiagnosed. With the availability of polymerase chain reaction and serology, the disease can be diagnosed even later in the course of the disease when culture results are often negative. The whole-cell pertussis vaccine dramatically reduced the incidence of the disease but fell into disrepute due to the rare serious neurologic side effects that led to the introduction of the acellular pertussis vaccine, which led to fewer adverse reactions and also proved to be safe and effective in the adolescent age group when used as a booster. However, the cost of the acellular vaccine is may be prohibitive for widespread use in the developing nations of the South East Asian region.     

Whooping cough in adults: an update on a reemerging infection

Pertussis, or whooping cough, which is commonly thought of as a pediatric illness, is an underappreciated adult pathogen. Recent outbreaks highlight the significance of pertussis in adults and the risk of transmission to at-risk infants who are most susceptible to complications, including death. This article describes the recent epidemiologic shifts and reviews the clinical presentation, diagnosis, and treatment of pertussis. New vaccination recommendations by the Advisory Committee on Immunization Practices in response to recent outbreaks and infant deaths are highlighted.     

Pertussis is a frequent cause of prolonged cough illness in adults and adolescents.

Although pertussis is increasingly recognized as a cause of prolonged cough illness in adolescents and adults, its prevalence is not well established. We evaluated pertussis infection in 442 adolescents and adults > or = 12 years old (mean age, 41.3 years) who had a cough-related illness of 7--56 days' duration. For 4 patients (0.9%), results of nasopharyngeal culture or PCR were positive for Bordetella pertussis; for 10 patients (2.3%), either results of culture or PCR were positive or pertussis antibody titers increased 4-fold. Eighty-eight patients (19.9%) had either laboratory-confirmed pertussis or laboratory evidence of pertussis. These patients had significantly longer duration of cough than did patients without laboratory evidence of pertussis (56 days vs. 46 days), and more of them had vomiting with cough (45.5% vs. 28.5%, respectively). Pertussis is a common cause of prolonged cough illness in adolescents and adults and is frequently associated with other symptoms of whooping cough.     

Consensus on the clinical and microbiologic diagnosis of Bordetella pertussis, and infection prevention. Expert Group on Pertussis Vaccination

Pertussis continues to be responsible for a significant disease burden worldwide. Although immunization practices have reduced the occurrence of the disease among children, waning vaccine- and infection-induced immunity still allows the disease to affect adolescents and adults who, in turn, can transmit the disease to non-immunized or partially immunized infants. This document is the result of a meeting in Mexico City of international experts who analyzed recent medical information in order to establish the current status of the epidemiology, diagnosis and surveillance of pertussis and, especially, the value of the dTpa booster dose in adolescents and adults as a pertussis prevention strategy in Mexico.     

Evolución de los casos de tosferina tras la vacunación de la embarazada y la pandemia COVID-19

BackgroundWhooping cough has had an increased incidence and severity specially in infants and maternal immunization has been implemented as a prevention strategy. COVID-19 pandemic seems to decrease the incidence of other respiratory diseases.MethodsRetrospective study from 2012 to 2021 to assess the influence of pertussis maternal immunizations and the first year of COVID-19 pandemic in the cases of whooping cough.Results960 suspected cases from primary care and hospital, with 130 cases (104 children and 26 adults) being diagnosed of whooping cough. In the post-vaccination period, a reduction in the cases and severity in infants up to 6 months old was observed as well as in the pertussis diagnosis in adult women. There were no whooping cough cases during the COVID-19 period.ConclusionsBoth the pertussis vaccination in pregnancy and the first year of the COVID-19 pandemic have decreased the number of pertussis cases.     

How best to estimate the global burden of pertussis?

In most countries, pertussis surveillance is inadequate for accurately estimating numbers of cases or deaths. Good estimates are needed to help set priorities for vaccination programmes. We aimed to develop a simple, reliable, and explicit method for estimating pertussis cases and deaths for children under 15 years to calculate the global disease burden in 1999. We estimated the proportion of susceptible children becoming infected in countries with poor vaccination coverage (<70%) in 1999 at 30% by 1 year, 80% by 5 years, and 100% by 15 years of age and for countries with good coverage (> or =70%) at 10% by 1 year, 60% by 5 years, and 100% by 15 years. Vaccine efficacy was estimated at 80% for preventing infection and 95% for preventing deaths. We used UN population estimates and vaccination coverage reported to WHO (adjusted for specific survey data if available). Case fatality ratios for countries with high and low child mortality were derived from published and unpublished work. For some countries with good vital events registration we used reported deaths adjusted for underascertainment. In 1999 there were an estimated 48.5 million pertussis cases in children worldwide. Deaths from pertussis were estimated at 390000 and at 295000 after adjustment for local data sources. Based on this approach, disability-adjusted life years from pertussis (12.7 million) in 2000 exceeded those of other preventable diseases such as lung cancer (11.4 million) and meningitis (5.8 million). This simple approach yields estimates that can be used for setting vaccination programme priorities. Better data are needed on the public health importance of pertussis in high mortality countries, the benefits of incomplete vaccination, and the harm from delayed vaccination.     

Patterns of susceptibility in an outbreak of Bordetella pertussis: Evidence from a community-based study.

OBJECTIVE: To describe an outbreak of Bordetella pertussis and to assess which factors were associated with the development of clinical pertussis in children and adults during the outbreak. DESIGN: A case series was described to define the epidemiology of the pertussis outbreak. A school-based survey of children was used to measure the incidence of clinical pertussis over the previous six months. Vaccination records from the local public health facility were used to look at the relationship between age and vaccination parameters, and susceptibility to clinically diagnosed pertussis. A cross-sectional survey of teachers, parents and some hospital workers was used to assess these associations in adults. SETTING: An outbreak of pertussis in an isolated northern community in British Columbia. POPULATION STUDIED: All children in the community who attend daycare, kindergarten or school, and their parents were surveyed. In addition, some health care workers and mothers of preschool children were surveyed. MAIN RESULTS: A total of 31 suspected cases of pertussis were identified over a three-month period. Ninety per cent of the affected children who had available vaccination records had received four or five doses of pertussis vaccine. Sixty per cent of the town's 209 children returned completed surveys. Of these, 69% had available vaccination records. Thirty-six children (28%) reported symptoms that fit the case definition for pertussis over the previous three months. Attack rates were highest for the group of children aged 10 to 14 years. In a multivariate logistic regression analysis, receiving prophylactic medication and an increased number of years from the last vaccine dose were found to be significant predictors for developing pertussis. Thirty-four per cent of the estimated 291 adults in the community returned completed surveys. The attack rate of pertussis in the adults was only 9%. Being a member of the school staff and/or having a household contact with pertussis were significant predictors of developing pertussis. CONCLUSIONS: Immunity to pertussis appears to wane during childhood. Peak susceptibility appears to be during early adolescence. Adults do not seem to be at greater risk than adolescents for developing the disease, but it seems unlikely that this is due to better immunity. Rather, it is probably related to a lower risk of exposure to pertussis and a lower rate of progression to symptomatic disease when adults are infected.     

Clinical manifestations of Bordetella pertussis infection in immunized children and young adults.

STUDY OBJECTIVES: The incidence and prevalence of pertussis in adults have increased in recent years. It has been shown that previously immunized adults and adolescents are the main sources of transmission of Bordetella pertussis. The aim of this study was to describe the clinical presentation and the clinical course of pertussis in children and young adults who were immunized previously against B pertussis. DESIGN: Retrospective study. SUBJECTS: Children and young adults who were reported by local physicians to the Department of Epidemiology in the Israeli Ministry of Health with serologically confirmed pertussis and who were immunized previously were included. Information sought included personal data, epidemiologic data, signs and symptoms, laboratory results, initial diagnosis, and treatment. RESULTS: In the 95 previously immunized patients with serologically confirmed pertussis (mean age [+/- SD], 8.9 +/- 4.4 years old; range, 5 to 30 years old), the mean duration from onset of symptoms until the final diagnosis of pertussis was 23 +/- 15 days. The disease was usually atypical and generally mild. All the described patients had cough, usually prolonged, lasting 4 +/- 3.6 weeks. Only 6% had the classic whoop. The mean WBC count was 8.7 +/- 2.6 cells/mm6, and the lymphocyte count was 40 +/- 12%. Two patients were admitted to the hospital for severe pneumonia. Among the reported cases, the proportion of patients between the ages of 10 and 45 years increased from 6.5% during the period from 1971 to 1980, to 26% during the period from 1980 to 1990, and to 38% during a 1989 outbreak. CONCLUSIONS: Pertussis in previously immunized individuals is usually characterized by an atypical and relatively mild clinical course. Patients suffer mainly from a prolonged and persistent cough. Early diagnosis may lead to prompt administration of therapy. Prophylaxis of exposed persons might be effective in decreasing both severity and transmission of the disease.