The current state of pertussis vaccination in pregnancy around the world, with recommendations for improved care: Consensus statements from the Global Pertussis Initiative.

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers.

Pertussis in India: Past, Present, and Future.

While vaccines have markedly reduced the incidence of pertussis, a resurgence has occurred in many countries. Until recently, pertussis has not been recognized as an important public health challenge in India due to its successful infant immunization program. However, India still accounts for a large proportion of the world's cases, and increasing reports of pertussis in other countries and in neonates have regenerated interest in pertussis among Indian authorities. The Global Pertussis Initiative (GPI) Annual Meeting was held virtually in October 2020, in part, to gain a better understanding of the epidemiology and disease burden of pertussis and to explore opportunities to improve its prevention in India. There was a consensus that pertussis cases are being underestimated in India due to multiple factors, such as a reliance on passive surveillance and diagnostic challenges. India offers both whole-cell pertussis and acellular pertussis vaccines, but vaccine coverage is inconsistent across regions due to differences in vaccine availability, access to health care, and regional administrative challenges. This report summarizes the outcomes and considers the key clinical implications of this meeting. The GPI agreed that active surveillance of pertussis in India would be optimal and recommended several studies, including serosurveillance among women of reproductive age to assess the prevalence of recent pertussis infection and to enable policy changes that will enhance the rational use of acellular and whole-cell vaccines. It also recommended engagement with nongovernmental organizations in order to encourage pregnancy immunization in the public sector. To achieve effective control of pertussis in the future, the GPI recognizes there are opportunities to characterize the burden of pertussis in India appropriately and increase vaccination coverage in multiple age groups.

Pertussis in Asia: Recent country-specific data and recommendations.

The Global Pertussis Initiative (GPI) Roundtable Meeting held in 2019, which preceded the COVID-19 pandemic, focused on the incidence, surveillance, and immunization practices for pertussis in the Asian region. Participants from China, India, Indonesia, Malaysia, Pakistan, Philippines, South Korea, Taiwan, and Thailand presented country-specific information on pertussis prevalence, diagnosis, surveillance, vaccine administration and schedules, maternal and neonatal disease rates, and policies and practice of vaccination during pregnancy. In recent years, many Asian countries have seen an increase in pertussis cases, although underreporting of the disease is a concern. Currently, most Asian countries have only passive surveillance for pertussis in place. There is a need for improved surveillance to determine the disease burden and justify vaccination policies and recommendations, such as essential vaccination, boosters, and vaccination during pregnancy. Better awareness of the disease in adolescents and adults is necessary, and infant and childhood vaccination schedules need to be improved in many countries. Differences between private versus public sector vaccination schedules and between whole-cell and acellular pertussis vaccines should continue to be examined. It can be anticipated that unmet needs in the prevention and management of pertussis will continue as the COVID-19 pandemic evolves and that key recommendations highlighted in this meeting report will be of ongoing importance.

Emerging macrolide resistance in Bordetella pertussis in mainland China: Findings and warning from the global pertussis initiative.

Whooping cough, or pertussis, is a highly communicable infectious disease caused by the bacterium Bordetella pertussis. Vaccination once reduced the incidence of the disease, but a global resurgence of the infection happened during the past two decades, likely due to the waning immunity of vaccination. Macrolides such as erythromycin and azithromycin are the drugs of primary choice for treatment. In this personal view, we call for attention to macrolide-resistant B. pertussis (MRBP), which has emerged and prevailed in mainland China for years and are exclusively mediated by mutations in the 23S rRNA gene. Whether the prevalence of MRBP in China results from overuse of azithromycin in clinical medicine remains unknown. The incidence of MRBP is low in other countries, but this could be a technical illusion since China employs culture as the mainstream diagnostic method whereas nucleic-acid amplification test being widely used in other countries fail to test antimicrobial susceptibility. Given the increasingly frequent global travel that facilitates microbial transmission worldwide, there is a pressing need to perform international surveillance on MRBP to prevent the potential circulation of the organism. Finding alternative agents that possess good activity against B. pertussis is also urgently required.

Recommendations to control pertussis prioritized relative to economies: A Global Pertussis Initiative update.

Pertussis is a vaccine-preventable disease that causes morbidity and mortality, particularly in infants and children <5 years of age. The Global Pertussis Initiative (GPI) recommendations represent a systematic evaluation and prioritization of strategies to prevent pertussis-related infant and child deaths, reduce global disease burden and prevent resurgence through vaccination strategies and public health policies at national, regional and local levels. The GPI recommendations are based on clinical trials and observational and surveillance data, which are essential in the planning, implementation and evaluation of vaccination practices and best use of available resources. Many low- and middle-income countries (LMIC) continue to use whole-cell pertussis (wP) vaccines for primary vaccination, while most high-income countries have replaced wP with the less-reactogenic acellular pertussis (aP) vaccines. This present manuscript pertains to discussions held during the GPI's meeting on November 11-13, 2016, in Cape Town, Republic of South Africa. The GPI recommends that LMIC aim for high coverage of infant series pertussis vaccines as a priority. In LMIC and countries with constrained vaccine funding, if wP vaccines are currently used, wP should continue to be used. Furthermore, given that protection against disease and death due to pertussis in neonates is a key priority of the GPI, it recommends that ap immunization in pregnancy should be implemented as a priority in all countries if resources allow. Given that surveillance and epidemiology data on which to base vaccine decisions are important, the GPI also suggests that, in areas where wP vaccines are implemented, standardization and calibration of wP vaccines are checked, considering the many different manufacturers and variable standards of production and quality control. In addition, as immunity to pertussis wanes following the primary infant series of vaccination, the GPI further recommends that toddlers, adolescents, healthcare and childcare workers receive booster vaccine doses, where resources allow.

Pertussis in Africa: Findings and recommendations of the Global Pertussis Initiative (GPI).

Pertussis remains a major cause of morbidity and mortality, particularly in infants and young children, and despite the availability of vaccines and pertinent national and international guidelines. The disease burden is more severe in low- and middle-income countries (LMICs), especially in the African continent. Pertussis is more prevalent among young infants in Africa. Poor or no pertussis surveillance, lack of disease awareness, diagnostic limitations, and competing health priorities are considered key contributory factors for this high pertussis burden in Africa. Most African countries use whole-cell pertussis (wP) vaccines, but coverage with three primary doses of diphtheria-tetanus-pertussis vaccines falls short of the World Health Organization's recommended goal of >90%. The Global Pertussis Initiative (GPI) works toward developing recommendations through systematic evaluation and prioritization of strategies to prevent pertussis-related infant and child deaths, as well as reducing global disease burden to acceptable national, regional, and local levels. For countries using wP vaccines, the GPI recommends continuing to use wP to improve primary and toddler booster vaccination coverage. Vaccination during pregnancy is the next priority when acellular pertussis (aP) vaccines and other resources are available that directly protect newborns too young to be vaccinated, followed by, in order of priority, booster doses in older children, adolescents, healthcare workers and finally, all adults. Improved surveillance should be a high priority for African LMICs assessing true disease burden and vaccine effectiveness to inform policy. More research is warranted to evaluate the safety and efficacy of wP and aP vaccines and strategies, and to determine their optimal use.

Long-lasting cough in an adult German population: incidence, symptoms, and related pathogens.

Studies of the incidence of pertussis in adults have shown that it accounts for only 5-15% cases of prolonged coughing. We assessed the burden of suffering related to prolonged coughing and tried to identify further causative agents. Based on a sentinel study with 35 general practitioners in two German cities (Krefeld, Rostock), with 3,946 patients fulfilling the inclusion criteria, we estimated the incidence of prolonged coughing in adults. In 975 of these outpatients, PCR and/or serology for adenovirus, Bordetella pertussis and B. parapertussis, human metapneumovirus, influenza virus A and rhinovirus, parainfluenza virus, Mycoplasma pneumonia, and respiratory syncytial virus (RSV) were performed. Treatment data were extracted for a subgroup of 138 patients. Descriptive statistics, including Kaplan-Maier curves were generated. Yearly incidence ranged between 1.4 and 2.1% per population in the two cities. Adult patients sought medical attention only after a median of 3 weeks of coughing. Irrespective of smoking and unrelated to the identified pathogens, the median duration of coughing was 6 weeks, with an interquartile range of 4-11 weeks. In 48.3% of patients, possible pathogens were identified, among which adenovirus (15.1%), RSV (7.5%), B. pertussis (5.6%), and influenza viruses (4.0%) were most often found. Symptoms were not indicative of a specific agent and a total of 64% of patients received antibiotics. Prolonged adult coughing requiring medical attention prompts substantial healthcare use. Apart from B. pertussis, a broad range of pathogens was associated with the symptoms. However, patients sought medical attention too late to guide efficacious therapeutic interventions using the diagnostic tests.

The protective role of maternally derived antibodies against Bordetella pertussis in young infants.

In 20 infants with polymerase chain reaction-confirmed pertussis <6 months of age, median cord blood anti-pertussis toxin, anti-filamentous hemagglutinin and anti-pertactin IgG antibody values were lower than in 80 matched controls: 10.5 versus 13.5 anti-pertussis toxin IU/mL, 14.5/18.0 (anti-filamentous hemagglutinin) and 6.0/9.0 (anti-pertactin), respectively. Although differences of median (and mean) antibody values between groups were not significant, they are in line with the concept of infant protection by maternal antibodies and thus support the strategy of pertussis booster immunization in pregnant women.

Rotavirus disease in Germany--a prospective survey of very severe cases.

OBJECTIVE: Rotavirus (RV) gastroenteritis is a notifiable disease in Germany. The reports to the authorities contain few data concerning the severity of disease. The aims of this study were to determine incidence and outcome of very severe cases of RV disease. METHODS: Cases of very severe RV disease were collected by the German Paediatric Surveillance Unit for rare diseases (Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland) using anonymous questionnaires based on hospitalized patients between April 2009 and March 2011. Inclusion criteria were detection of RV antigen in feces, patient aged 0-16 years and 1 or more of the following criteria: intensive care treatment, hypernatremia or hyponatremia (>155 mmol/L or <125 mmol/L), clinical signs of encephalopathy (somnolence, seizures, apnea) and RV-associated death. RESULTS: During 2 years, 130 cases of very severe RV disease were reported, 101 of 130 were verified. Seventeen patients had nosocomial infection, of whom 14 were neonates in intensive care. Among those, 12 infants had verified or suspected necrotizing enterocolitis. Eighty-four community-acquired cases were reported, median age was 10.5 months (0-108 months). The median hospital stay was 6 days, and 48 patients needed intensive care treatment. Among children less than 5 years of age, the yearly incidence of community-acquired very severe RV disease was 1.2 of 100,000 (95% confidence interval: 0.9-1.4/100,000). A total of 26 of 84 and 10 of 84 patients had severe hypernatremia or hyponatremia, respectively, and 58 of 84 patients had signs of encephalopathy. Three deaths were reported (1 nosocomial and 2 community acquired). CONCLUSIONS: RV infection in Germany can have a life-threatening course. A substantial number are nosocomial infections.

Pertussis control in the Asia-Pacific region: a report from the Global Pertussis Initiative.

The Global Pertussis Initiative (GPI) is an expert, scientific forum that seeks to address the worldwide burden of pertussis. To reduce the global incidence of pertussis, the GPI recommends reinforcing and/or improving current infant and toddler immunization strategies, universal booster dosing of pre-school children, universal booster dosing of adolescents and adults (where appropriate), and cocooning to protect infants. To tailor these global recommendations to local needs, the GPI has hosted two meetings in Asia-Pacific. Pertussis vaccination practices differ across Asia-Pacific, with only some countries recommending booster dosing. Given the limited use of laboratory diagnostics, disease surveillance was considered inadequate. To make informed health policy decisions on pertussis prevention, more robust epidemiological data are needed. Because of its unique clinical presentation, adolescent and adult pertussis is under-recognized by lay and medical communities. Consequently, adolescent and adult disease likely exists even in Asian-Pacific countries where epidemiological data are presently lacking. In Asia-Pacific, there exist issues with health care access and costs. Fragmented health care will negatively impact the effectiveness of any proposed immunization strategies. The GPI recommends-in Asia-Pacific and elsewhere-that countries first educate lay and medical communities on pertussis, while simultaneously implementing robust surveillance practices. Once armed with sufficient epidemiological evidence, the prevention strategies recommended by the GPI can then be appropriately (and more effectively) introduced.

Effect of Safety Measures on Bacterial Contamination Rates of Blood Components in Germany.

SUMMARY: Requirements for bacterial testing of blood components on a defined quantity as part of routine quality control were introduced in Germany by the National Advisory Committee Blood of the German Federal Ministry of Health in 1997. The philosophy was to establish standardized methods for bacterial testing. Numerous measures to reduce the risk of bacterial contamination were implemented into the blood donation and manufacturing processes between 1999 and 2002. German Blood establishments performed culture-based bacterial testing on random samples of platelet concentrates (PCs), red blood cells (RBCs) and fresh frozen plasma (FFP) and reported data out of the production periods 1998, 2001 and 2005/2006. While the bacterial contamination rate of apheresis PCs remained nearly unchanged, it decreased by 70% for pooled PCs to a rate of 0.158% in the last observation period. Leukocyte-depleted RBCs with diversion of the initial blood volume showed a contamination rate of 0.029% which is significantly lower than that of RBCs without leukocyte depletion and diversion (0.157%). The contamination rate of plasma decreased by 80%. Preventive measures resulted in a significant reduction of bacterial contamination of blood components. Long-term monitoring with standardized methods for bacteria testing supports evaluation of the cumulative effect of contamination reducing measures.

Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children.

We measured IgA and IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in sera from 203 1-year-old children who had received one to three doses of a monocomponent PT toxoid vaccine. Ten children (5%) had IgA antibody to PT indicating recent infection; seven of these children had received three doses of vaccine. PT IgA responders did not have significantly longer coughing episodes than PT IgA non-responders. Since an IgA antibody response occurs in only approximately 50% of infected children, the actual infection rate in our cohort is estimated to approximately 10%. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine should be undertaken.

Pertussis sources of infection and routes of transmission in the vaccination era.

Vaccination against pertussis has resulted in reduction of the infection pressure of Bordetella pertussis (partial herd immunity), but the circulation of B. pertussis has persisted as a consequence of waning of vaccine-induced and naturally acquired immunity. An increase in the reported incidence of B. pertussis infection in older children, adolescents and young adults has been noted, resulting in a perceived resurgence of the disease in these age groups. Regardless of whether this resurgence is real or not, older groups are increasingly recognized as playing an important role in transmitting B. pertussis infection to incompletely immunized infants, in whom pertussis disease continues to cause severe and fatal illness, albeit at much lower levels than in the prevaccine era. Several studies have suggested that mothers, in particular, are a significant source of infection for infants. Adolescents, grandparents and health care workers can also play a role. By contrast, most adolescents acquire the infection from schoolmates and friends, whereas for adults the main sources are children and work colleagues. Furthermore teachers, child care workers and health care workers could be at increased risk of being exposed to, and transmitting, B. pertussis infection. Current immunization strategies inadequately control the circulation of B. pertussis, in part because of suboptimal adherence to current pediatric immunization guidelines. In addition to efforts to improve pertussis immunization rates in children, the expansion of pertussis immunization to target specific groups should be considered. Besides reducing morbidity in the targeted groups, these strategies could decrease the residual burden of pertussis morbidity and mortality in infants.

Health burden of pertussis in infants and children.

In countries with high rates of vaccination against pertussis, the incidence of this disease has decreased dramatically compared with the prevaccine era. However, pertussis still occurs in these countries, and severe morbidity and mortality are greatest among infants, particularly those who are unimmunized or incompletely immunized. Pertussis in older children and adults is perceived by many as being a mild disease, but it is a significant health burden in persons of all ages. Infants with pertussis experience the highest rates of hospitalization, complications and death. Severe complications include pneumonia, encephalopathy and meningoencephalitis. In addition, infants may experience weight loss, bronchitis, otitis media, apnea, cyanosis, inguinal hernia and rectal prolapse. It is essential to explore methods to prevent disease transmission to infants in the months before they complete their primary immunization series. The Global Pertussis Initiative was established to assess the true health burden of pertussis in infants and to suggest strategies to combat transmission and infection with Bordetella pertussis, which remains a significant public health concern.

Use of antibiotics in the prevention and treatment of pertussis.

Antibiotics are commonly used for treating confirmed cases of pertussis and also for disease prevention in outbreak situations, and there is little evidence of antibiotic resistance of Bordetella pertussis. The most commonly used antibiotic is erythromycin, but the associated side effects limit compliance and therefore efficacy. Other antibiotics, such as clarithromycin and azithromycin, have been shown to be at least as effective as erythromycin in preventing and treating pertussis, and they also have fewer side effects, which improves compliance. This article outlines the use of different antibiotics in pertussis management and their effect on preventing disease transmission and reducing disease severity and duration.