The Fim and FhaB adhesins play a crucial role in nasal cavity infection and Bordetella pertussis transmission in a novel mouse catarrhal infection model.

Pulmonary infections caused by Bordetella pertussis used to be the prime cause of infant mortality in the pre-vaccine era and mouse models of pertussis pneumonia served in characterization of B. pertussis virulence mechanisms. However, the biologically most relevant catarrhal disease stage and B. pertussis transmission has not been adequately reproduced in adult mice due to limited proliferation of the human-adapted pathogen on murine nasopharyngeal mucosa. We used immunodeficient C57BL/6J MyD88 KO mice to achieve B. pertussis proliferation to human-like high counts of 108 viable bacteria per nasal cavity to elicit rhinosinusitis accompanied by robust shedding and transmission of B. pertussis bacteria to adult co-housed MyD88 KO mice. Experiments with a comprehensive set of B. pertussis mutants revealed that pertussis toxin, adenylate cyclase toxin-hemolysin, the T3SS effector BteA/BopC and several other known virulence factors were dispensable for nasal cavity infection and B. pertussis transmission in the immunocompromised MyD88 KO mice. In contrast, mutants lacking the filamentous hemagglutinin (FhaB) or fimbriae (Fim) adhesins infected the nasal cavity poorly, shed at low levels and failed to productively infect co-housed MyD88 KO or C57BL/6J mice. FhaB and fimbriae thus appear to play a critical role in B. pertussis transmission. The here-described novel murine model of B. pertussis-induced nasal catarrh opens the way to genetic dissection of host mechanisms involved in B. pertussis shedding and to validation of key bacterial transmission factors that ought to be targeted by future pertussis vaccines.

Tosferina en el adulto: el enemigo visible / Whooping Cough: The Visible Enemy

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[Translated article] Whooping Cough: The Visible Enemy / Tosferina en el adulto: el enemigo visible

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Emerging and Re-emerging Infections in Children: COVID/ MIS-C, Zika, Ebola, Measles, Varicella, Pertussis ... Immunizations.

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal.

Infant rhesus macaques as a non-human primate model of Bordetella pertussis infection.

BACKGROUND: The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s-1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved. METHODS: In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis. RESULTS: Upon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p. CONCLUSION: These results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.

Seasonal Bordetella pertussis pattern in the period from 2008 to 2018 in Germany.

BACKGROUND: After the introduction of a vaccine against B. pertussis the seasonal pattern with the highest number of infections in the spring to summer months changed. Recent studies from around the world suggest that B. pertussis infections again follow a seasonal pattern with increased incidence in summer.The aim of this study was to investigate whether respiratory infections caused by B. pertussis in the period from January 2008 to December 2018 also seasonally spread in Germany and if so, when the B. pertussis activity peaked. METHODS: We tested 19,031 samples, mainly from Southern Germany, collected in the period from January 2008 to December 2018 using a Multiplex PCR assay. We assessed the number and proportion of samples positive for B. pertussis, stratified by patient's age and month. The seasonal distribution was investigated by plotting the average proportion of positive samples for each month. RESULTS: We observed a B. pertussis seasonality with the highest number of positive samples in the months from June until September. In contrast, testing of samples for B. pertussis was requested most frequently in the period from October until March. The proportion of positive samples increased earlier in adolescents (age 10 to 19) than in other age groups. CONCLUSIONS: We found a seasonality of B. pertussis infections in Germany, which differs from the time when most samples are sent in for testing of B. pertussis. Our study suggests that clinicians should be more aware of B. pertussis infections in the months from June until September to prevent further transmission to vulnerable family members.

Transmission of respiratory tract infections at mass gathering events.

PURPOSE OF REVIEW: Mass gathering events bring people from across all continents increasing the risk of spread of aerosol transmissible respiratory tract infections. Respiratory tract infections for instance in pilgrims attending the world's largest recurring annual pilgrimage, the Hajj are common. We review recent literature on viral and bacterial infectious diseases with special focus on the Hajj. RECENT FINDINGS: The prevalence of bacterial and viral infections continue to increase, because of the acquisition of rhinovirus, coronaviruses (229E, HKU1, OC43), influenza A H1N1, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus during Hajj. Whilst MERS-CoV continues to circulate in the Middle East, no cases of MERS-CoV have yet been identified in pilgrims during Hajj. SUMMARY: Respiratory tract infections are a major cause of morbidity in pilgrims attending mass gathering events. The management of severe respiratory infections should consider investigation and empirical coverage for the most likely agents based on syndromic surveillance data from hosting country and /or other relevant exposure history during events. Pneumococcal and Pertussis vaccines should be recommended for Hajj pilgrims.

Pertussis over two decades: seroepidemiological study in a large population of the Siena Province, Tuscany Region, Central Italy.

OBJECTIVES: To evaluate seroprevalence against Bordetella pertussis in Tuscany, a large Italian region, from 1992 to 2005 and from 2013 to 2016. DESIGN: Seroepidemiological study. PARTICIPANTS: 1812 serum samples collected in Tuscany from subjects older than 12 years from 1992 to 2005 and from 2013 to 2016. OUTCOME MEASURES: Specific antibody levels were determined by means of standard commercial ELISA using a dual cut-off of 50 and 125 IU/mL as markers of past and recent infection/vaccination, respectively. RESULTS: The highest values of IgG titres were observed in 1992-1994 in all subjects (69.5 IU/mL), with prevalence values of subjects with IgG titres of >50 and >125 IU/mL of 68.3% and 23.8%, respectively. IgG titres decreased in the years thereafter (37.8 IU/mL in 2002-2005), together with prevalence values (41.7% and 8.1% in 2002-2005). In 2013-2016, both IgG titres and prevalence values showed a slight increase (50.6 IU/mL, 53.9% and 14.7%, respectively). IgG titres and prevalence followed the same age-related trend in all time periods considered, with the highest values in subjects aged 12-22 years. The lowest values were found in the age group of subjects aged 23-35 years (OR 0.54). CONCLUSIONS: Since 2002, approximately half of the population over 22 years of age have low IgG titres and are presumably susceptible to acquiring and transmitting pertussis infection. In addition, in 2013-2016, almost one-third of subjects aged 12-22 years, that is, the age group most likely to have been vaccinated against pertussis in infancy, had low antibody levels. Improving vaccination coverage and implementing careful surveillance are therefore recommended in order to prevent morbidity and mortality due to pertussis.

Pertussis, historia, hechos y situación actual / Pertussis, history, facts, and current situation / Pertussis, história, fatos e situação atual

Pertussis, tos convulsa o coqueluche son términos que se emplean como sinónimos para referirse a una infección respiratoria inmunoprevenible grave causada por la bacteria gram negativa denominada Bordetella pertussis. La mejor manera de prevenir la enfermedad es a través de la vacunación. Las primeras experimentaciones con vacunas comenzaron después de que Jules Bordet y Octave Gengou del Instituto Pasteur de Bruselas identificaran el agente etiológico en 1906. Estas primeras vacunas se hicieron a partir de células enteras del agente causal muertas por calor. La historia de las vacunas contra la enfermedad continuó desde aquel entonces con vacunas combinadas y luego con vacunas de componentes o acelulares. Su uso masivo desde los años 50 permitió una reducción muy marcada de la morbimortalidad asociada a la enfermedad. Sin embargo en el año 2008, se estimó que en el mundo se producen por año 16 millones de casos de los cuales 195.000 resultan ser fatales. Para el año 2014 esta estimación sobre el número de casos creció a 24,1 millones de casos en el año. El incremento del número de casos detectado en los últimos 20 años ha estado dirigiendo la mirada de la comunidad sanitaria y científica hacia la identificación de causas de esta nueva situación epidemiológica de pertussis para revisar e implementar estrategias de control más efectivas. Se ha logrado así un mejor reconocimiento de la enfermedad no solo entre los lactantes y los niños, sino también en los adolescentes y adultos. El mayor reconocimiento de que los niños mayores, los adolescentes y los adultos están en riesgo de contraer la enfermedad y que pueden transmitirla a los más vulnerables ha resaltado la necesidad de comprender mejor la inmunidad inducida por las vacunas y su duración. El rol de las vacunas y en particular de las vacunas acelulares constituidas por pocos inmunógenos en altas dosis sobre la selección de geno/fenotipos bacterianos más resistentes a la inmunidad inducida por las vacunas ha comenzado a visualizarse más claramente. La investigación en curso que utiliza herramientas novedosas sin dudas ha mejorado el conocimiento en general sobre esta patología, sin embargo la investigación debe continuar de forma de lograr una vigilancia más oportuna con terapias y vacunas de nueva generación más eficaces.

Pertussis or whooping cough is a preventable respiratory infectious disease caused by the gram-negative microorganism known as Bordetella pertussis. The best strategy to prevent pertussis is to get vaccinated. Vaccine development began just after Jules Bordet and Octave Gengou at Pasteur Institute from Brussels identified the etiologic agent of the disease in 1906. The first vaccine was formulated with heat-killed B. pertussis bacteria, which was later combined with tetanus and diphtheria toxoids (DTP). The second generation of pertussis vaccine was the acellular vaccine consisting in a few purified B. pertussis immunogens. The massive use of these vaccines since the 50s reduced the morbidity and mortality associated with the disease. However, in 2008 it was estimated that 16 million cases occurred by year with 195,000 deaths worldwide. For 2014, this estimation rised to 24.1 million cases per year. The increase in the number of cases detected in the last 20 years has been directing the attention of the health and scientific community towards the identification of causes of this new epidemiological situation of pertussis to review and implement more effective control strategies. This has achieved a better recognition of the disease not only among infants and children but also in adolescents and adults. The awareness that older children, adolescents and adults are at risk of contracting the disease and that they can transmit pertussis to the most vulnerable highlighted the need to better understand the immunity induced by pertussis vaccination and also the duration of such immunity. Another aspect that needs to be understood is that related to the selection pressure that the vaccines would be exerting (in particular the acellular vaccines) on the circulating bacterial population. In this sense, an increase in the prevalence of strains of B. pertussis that are more resistant to the immunity conferred by the vaccines has been detected. The ongoing research using innovative tools has undoubtedly improved the knowledge on pertussis; however research should continue to achieve a more timely surveillance with more effective new generation therapies and vaccines.

Pertussis, tosse convulsa ou coqueluche são termos que se utilizam como sinônimos para fazer referência a uma infecção respiratória imunoprevenível grave provocada pela bactéria gram negativa denominada Bordetella pertussis. A melhor forma de prevenir a doença é através da vacinação. As primeiras experimentações com vacinas começaram depois de que Jules Bordet e Octave Gengou do Instituto Pasteur de Bruxelas identificassem o agente etiológico em 1906. Estas primeiras vacinas foram feitas a partir de células inteiras do agente causal mortas por calor. A história das vacinas contra a doença continuou a partir de então com vacinas combinadas e depois com vacinas de componentes ou acelulares. O uso generalizado delas desde os anos 50 permitiu uma redução muito importante da morbimortalidade associada à doença. Entretanto, no ano 2008, a estimativa foi de 16 milhões de casos produzidos no mundo por ano dos quais 195.000 resultaram fatais. Para o ano 2014, essa estimativa sobre o número de casos cresceu a 24,1 milhões de casos no ano. O aumento do número de casos detectado nos últimos 20 anos dirigiu e dirige o foco da comunidade sanitária e científica para a identificação de causas dessa nova situação epidemiológica de coqueluche de forma de revisar e implementar estratégias de controle mais efetivas. Um melhor reconhecimento da doença foi assim possível, não só entre bebês e meninos, mas também nos adolescentes e adultos. O maior reconhecimento de que as crianças mais velhas, os adolescentes e os adultos estão em risco de contrair a doença e que pode transmiti-la aos mais vulneráveis tem salientado a necessidade de compreender melhor a imunidade induzida pelas vacinas e a duração delas. O papel das vacinas e, em particular, das vacinas acelulares constituídas por poucos imunógenos em altas doses sobre a seleção de genótipos/fenótipos bacterianos mais resistentes à imunidade induzida pelas vacinas tem começado a ser visualizado mais claramente. A pesquisa em andamento que utiliza ferramentas novas, sem dúvidas, tem melhorado o conhecimento em geral sobre essa patologia, contudo a pesquisa deve continuar de maneira de alcançar uma vigilância mais oportuna com terapias e vacinas de nova geração mais eficazes.

Genome characteristics of Bordetella pertussis isolates from Tunisia.

The recent increase in pertussis cases observed in some countries may have several causes, including the evolution of Bordetella pertussis populations towards escape of vaccine-induced immunity. Most genomic studies of B. pertussis isolates performed so far are from countries that use acellular vaccines. The objective was to analyse genomic sequences of isolates collected during the 2014 whooping cough epidemic in Tunisia, a country where whole-cell vaccines are used. Ten Tunisian isolates and four vaccine strains were sequenced and compared to 169 isolates from countries where acellular vaccines are used. Phylogenetic analysis showed that Tunisian isolates are diverse, demonstrating a multi-strain 2014 epidemic peak, and are intermixed with those circulating in other world regions, showing inter-country transmission. Consistently, Tunisian isolates have antigen variant composition observed in other world regions. No pertactin-deficient strain was observed. The Tunisian B. pertussis population appears to be largely connected with populations from other countries.

Duration of Immunity and Effectiveness of Diphtheria-Tetanus-Acellular Pertussis Vaccines in Children.

Importance: The United States has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high estimated vaccine coverage. Short-lived immunity induced by diphtheria-tetanus-acellular pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden, but the duration of protection conferred by DTaP vaccines remains incompletely quantified. Objective: To assess the duration of immunity and the effectiveness of DTaP vaccines in US children. Design, Setting, and Participants: A mathematical, age-structured model of pertussis transmission, previously validated empirically on incidence data in Massachusetts, was used in this simulation study to assess the duration of DTaP immunity most consistent with the empirical values of the relative increase in the odds of acquiring pertussis from recent epidemiologic studies in the United States. The study included 5 simulated cohorts of children born between January 1, 2001, and December 31, 2005, followed up between the ages of 5 and 9 years (study period, January 1, 2006, to December 31, 2014). Statistical analysis was performed from May 1 to December 1, 2017. Interventions: Vaccination with DTaP according to the US immunization schedule, with a range of assumptions regarding the degree of waning immunity. Main Outcomes and Measures: Vaccine effectiveness and relative change in the odds of acquiring pertussis (odds ratio) in children aged 5 to 9 years, duration of DTaP immunity, and vaccine population-level impact. Results: This study found a marked association between the degree of waning immunity, vaccine effectiveness, and the odds ratio. Counterintuitively, the odds ratio was positively associated with vaccine effectiveness, as a consequence of nonlinear, age-assortative transmission dynamics. Based on the empirical odds ratios (1.33; 95% CI, 1.23-1.43), it was estimated that vaccine effectiveness exceeded 75% in children aged 5 to 9 years and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose. Conclusions and Relevance: The results of this study suggest that temporal trends in the odds of acquiring pertussis are an unreliable measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. Control strategies should be based on the best available estimates of vaccine properties and the age structure of the transmission network.

Resurgence of Pertussis Infections in Shandong, China: Space-Time Cluster and Trend Analysis.

Although vaccination is effective in preventing infection, pertussis remains endemic worldwide, including China. To lead better targeted prevention strategies, we examined dynamics of spatial and temporal patterns of pertussis transmission in Shandong, China, from 2009 to 2017. We used space-time cluster analysis, logistic regression analysis, and regression tree model to detect the changes in spatial patterns of pertussis infections in Shandong Province, China, between periods (2009-2011, 2012-2014, and 2015-2017). The yearly pertussis incidence rates dramatically increased by 16.8 times from 2009 to 2017. Shifting patterns of peaks of pertussis infections were observed over both time (from June-July to August-September) and space (from Linyi to Jinan), with increasing RR from 4.1 (95% CI: 2.3-7.4) (2009-2011) to 6.1 (95% CI: 5.6-6.7) (2015-2017) and obvious coincidence of peak time. West Shandong had larger odds of increased infections over the study period (odds ratio: 1.52 [95% CI: 1.05-2.17]), and pertussis had larger odds of spreading to east (odds ratio: 2.32 [95% CI: 1.63-3.31]) and north (odds ratio: 1.69 [95% CI: 1.06-2.99]) over time. Regression tree model indicated that the mean difference in yearly average pertussis incidence between 2009-2011 and 2015-2017 increased by more than 4-fold when the longitudes of counties are < 118.0°E. The geographic expansion of pertussis infection may increase the risk of epidemic peaks, coinciding with increased infections in the future. The findings might offer evidence for targeting preventive measures to the areas most in need to minimize the impact of the disease.

Pertussis: The Identify, Isolate, Inform Tool Applied to a Re-emerging Respiratory Illness.

Pertussis, commonly referred to as "whooping cough," is a highly contagious acute respiratory infection that has exhibited cyclical outbreaks throughout the last century. Although vaccines have provided some immunity, many populations, including infants and pregnant women, remain at risk for serious illness. Through the use of the novel "Identify, Isolate, Inform" (3I) tool, emergency department (ED) providers can readily recognize key symptoms of the disease and risk factors for exposure, thus curbing its transmission through early initiation of antimicrobial therapy and post-exposure prophylaxis. The three classic stages of pertussis include an initial catarrhal stage, characterized by nonspecific upper respiratory infection symptoms, which may advance to the paroxysmal stage, revealing the distinctive "whooping cough." This cough can persist for weeks to months leading into the convalescent stage. Household contacts of patients with suspected pertussis or other asymptomatic, high-risk populations (infants, pregnant women in their third trimester, and childcare workers) may benefit from post-exposure prophylactic therapy. The Pertussis 3I tool can also alert healthcare professionals to the proper respiratory droplet precautions during contact with a symptomatic patient, as well as isolation practices until antimicrobial treatment is in progress. ED personnel should then inform local public health departments of any suspected cases. All of these actions will ultimately aid public health in controlling the incidence of pertussis cases, thus ensuring the protection of the general public from this re-emerging respiratory illness.

Attributes influencing parental decision-making to receive the Tdap vaccine to reduce the risk of pertussis transmission to their newborn - outcome of a cross-sectional conjoint experiment in Spain and Italy.

Pertussis vaccination of parents and household contacts ('cocooning') to protect newborn infants is an established strategy in many countries, although uptake may be low. Many aspects may influence such decision-making. We conducted a cross-sectional survey (NCT01890447) of households and other close contacts of newborns aged ≤6 months (or of expectant mothers in their last trimester) in Spain and Italy, using an adaptive discrete-choice experiment questionnaire. Aims were to assess the relative importance of attributes influencing vaccine adoption, and to estimate variation in vaccine adoption rates and the impact of cost on vaccination rates. Six hundred and fifteen participants (Spain, n = 313; Italy, n = 302) completed the survey. Of 144 available questionnaire scenarios, the most frequently selected (14% of respondents in both countries) were infant protection by household vaccination at vaccination center, recommendation by family physician and health authorities, with information available on leaflets and websites. The attribute with highest median relative importance was 'reduction in source of infection' in Spain (23.1%) and 'vaccination location' in Italy (18.8%). Differences between other attributes were low in both countries, with media attributes showing low importance. Over 80% of respondents indicated a definite or probable response to vaccine adoption (at no-cost) with estimated probability of adoption of 89-98%; applying vaccine costs (25€ per person) would reduce the probability of uptake by 7-20% in definite/probable respondents. Awareness of these determinants is helpful in informing Health Authorities and healthcare practitioners implementing a cocooning strategy for those populations where maternal immunization is not a preferred option.

PERISCOPE: road towards effective control of pertussis.

The resurgence and changing epidemiology of pertussis in high-income countries, the high infant mortality caused by pertussis in low-income countries, and the increasing morbidity in all age groups worldwide call for a concerted effort to both improve the current vaccines and develop new vaccines and vaccination strategies against pertussis. In this Personal View, we identify several key obstacles on the path to developing a durable solution for global control of pertussis. To systematically address these obstacles, the PERtussIS Correlates Of Protection Europe (PERISCOPE) Consortium was established in March, 2016. The objectives of this consortium are to increase scientific understanding of immunity to pertussis in humans induced by vaccines and infections, to identify biomarkers of protective immunity, and to generate technologies and infrastructure for the future development of improved pertussis vaccines. By working towards the accelerated licensure and implementation of novel, well tolerated, and effective pertussis vaccines, we hope to strengthen and stimulate further collaboration and transparency between the key stakeholders, including the public, the scientific community, public health institutes, regulatory authorities, and vaccine manufacturers.

Prospective multinational serosurveillance study of Bordetella pertussis infection among 10- to 18-year-old Asian children and adolescents.

OBJECTIVES: Bordetella pertussis continues to cause outbreaks worldwide. To assess the role of children and adolescent in transmission of pertussis in Asia, we performed a multinational serosurveillance study. METHODS: From July 2013 to June 2016, individuals aged 10 to 18 years who had not received any pertussis-containing vaccine within the prior year were recruited in 10 centres in Asia. Serum anti-pertussis toxin (PT) IgG was measured by ELISA. Demographic data and medical histories were obtained. In the absence of pertussis immunization, anti-PT IgG ≥62.5 IU/mL was interpreted as B. pertussis infection within 12 months prior, among them levels ≥125 IU/mL were further identified as infection within 6 months. RESULTS: A total of 1802 individuals were enrolled. Anti-PT IgG geometric mean concentration was 4.5, and 87 (4.8%) individuals had levels ≥62.5 IU/mL; among them, 73 (83.9%) had received three or more doses of pertussis vaccine before age 6 years. Of 30 participants with persistent cough during the past 6 months, one (3.3%) had level ≥125 IU/mL. There was no significant difference in proportions with anti-PT IgG ≥62.5 IU/mL among age groups (13-15 vs. 10-12 years, 16-18 vs. 10-12 years), between types of diphtheria, pertussis and tetanus (DTP; whole cell vs. acellular), number of doses before age 6 years within the DTP whole-cell pertussis vaccine (five vs. four doses) or acellular pertussis vaccine (five vs. four doses) and history of persistent cough during the past 6 months (yes vs. no). CONCLUSIONS: There is significant circulation of B. pertussis amongst Asian children and adolescents, with one in 20 having serologic evidence of recent infection regardless of vaccination background.

In vivo imaging of bacterial colonization of the lower respiratory tract in a baboon model of Bordetella pertussis infection and transmission.

Recent whooping cough (pertussis) outbreaks in many countries highlight the crucial need for a better understanding of the pathogenesis of Bordetella pertussis infection of the respiratory tract. The baboon is a recently described preclinical model for the study of B. pertussis infection and may be ideal for the evaluation of new pertussis vaccines. However, many pathophysiological aspects, including bacterial localization and interactions, have yet to be described in this model. Here, we used a baboon model of infection with a fluorescent GFP-expressing B. pertussis strain, derived from European clinical isolate B1917. Juvenile baboons were used to evaluate susceptibility to infection and transmission. Non-invasive in vivo imaging procedures, using probe-based confocal endomicroscopy coupled with bronchoscopy, were developed to track fluorescent bacterial localization and cellular interactions with host cells in the lower respiratory tract of infected animals. All B1917-GFP-challenged animals developed classical pertussis symptoms, including paroxysmal cough, nasopharyngeal colonization, and leukocytosis. In vivo co-localization with antigen presenting cells and progressive bacterial colonization of the lower airways were also assessed by imaging during the first weeks of infection. Our results demonstrate that in vivo imaging can be used to assess bacterial colonization and to point out interactions in a baboon model of pertussis.

Close encounters between infants and household members measured through wearable proximity sensors.

Describing and understanding close proximity interactions between infant and family members can provide key information on transmission opportunities of respiratory infections within households. Among respiratory infections, pertussis represents a public health priority. Pertussis infection can be particularly harmful to young, unvaccinated infants and for these patients, family members represent the main sources of transmission. Here, we report on the use of wearable proximity sensors based on RFID technology to measure face-to-face proximity between family members within 16 households with infants younger than 6 months for 2-5 consecutive days of data collection. The sensors were deployed over the course of approximately 1 year, in the context of a national research project aimed at the improvement of infant pertussis prevention strategies. We investigated differences in close-range interactions between family members and we assessed whether demographic variables or feeding practices affect contact patterns between parents and infants. A total of 5,958 contact events were recorded between 55 individuals: 16 infants, 4 siblings, 31 parents and 4 grandparents. The aggregated contact networks, obtained for each household, showed a heterogeneous distribution of the cumulative time spent in proximity with the infant by family members. Contact matrices defined by age and by family role showed that most of the contacts occurred between the infant and other family members (70%), while 30% of contacts was among family members (infants excluded). Many contacts were observed between infants and adults, in particular between infant and mother, followed by father, siblings and grandparents. A larger number of contacts and longer contact durations between infant and other family members were observed in families adopting exclusive breastfeeding, compared to families in which the infant receives artificial or mixed feeding. Our results demonstrate how a high-resolution measurement of contact matrices within infants' households is feasible using wearable proximity sensing devices. Moreover, our findings suggest the mother is responsible for the large majority of the infant's contact pattern, thus being the main potential source of infection for a transmissible disease. As the contribution to the infants' contact pattern by other family members is very variable, vaccination against pertussis during pregnancy is probably the best strategy to protect young, unvaccinated infants.

Management and control of communicable diseases in schools and other child care settings: systematic review on the incubation period and period of infectiousness.

BACKGROUND: Information on the incubation period and period of infectiousness or shedding of infectious pathogens is critical for management and control of communicable diseases in schools and other childcare settings. METHODS: We performed a systematic literature review (Pubmed and Embase) to identify and critically appraise all relevant published articles using incubation, infectiousness or shedding, and exclusion period as parameters for the search. No language, time, geographical or study design restrictions were applied. RESULTS: A total of 112 articles met the eligibility criteria. A relatively large number were retrieved for gastrointestinal diseases and influenza or respiratory syncytial virus, but there were few or no studies for other diseases. Although a considerable number of publications reported the incubation and shedding periods, there was less evidence concerning the period of infectiousness. On average, five days of exclusion is considered for measles, mumps, rubella, varicella and pertussis. For other diseases, such as most cases of meningococcal disease, hepatitis A and influenza exclusion is considered as long as severe symptoms persist. However, these results are based on a diverse range of study characteristics, including age, treatment, vaccination, underlying diseases, diagnostic tools, viral load, study design and definitions, making statistical analysis difficult. CONCLUSIONS: Despite inconsistent definitions for key variables and the diversity of studies reviewed, published data provide sufficient quantitative estimates to inform decision making in schools and other childcare settings. The results can be used as a reference when deciding about the exclusion of a child with a communicable disease that both prevents exposure and avoids unnecessary absenteeism.