Reinvestigating the Coughing Rat Model of Pertussis To Understand Bordetella pertussis Pathogenesis.

Bordetella pertussis is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP, DTaP, and Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the reemergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. The emergence of genetically diverging strains, combined with waning aP vaccine efficacy, calls for reevaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged 7-week-old Sprague-Dawley rats with 108 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of B. pertussis infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole-body plethysmography. Onset of cough occurred between 2 and 4 days after B. pertussis challenge, averaging five coughs per 15 min, with peak coughing occurring at day 8 postinfection, averaging upward of 13 coughs per 15 min. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days postchallenge. The rats exhibited increased bronchial restriction following B. pertussis infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-B. pertussis IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between B. pertussis strains.

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.

Identfication of viral and bacterial etiologic agents of the pertussis-like syndrome in children under 5 years old hospitalized.

BACKGROUND: Acute respiratory infections (ARIs) represent an important cause of morbidity and mortality in children, remaining a major public health concern, especially affecting children under 5 years old from low-income countries. Unfortunately, information regarding their epidemiology is still limited in Peru. METHODS: A secondary data analysis was performed from a previous cross-sectional study conducted in children with a probable diagnosis of Pertussis from January 2010 to July 2012. All samples were analyzed via Polymerase Chain Reaction (PCR) for the following etiologies: Influenza-A, Influenza-B, RSV-A, RSV-B, Adenovirus, Parainfluenza 1 virus, Parainfluenza 2 virus, Parainfluenza 3 virus, Mycoplasma pneumoniae and Chlamydia pneumoniae. RESULTS: A total of 288 patients were included. The most common pathogen isolated was Adenovirus (49%), followed by Bordetella pertussis (41%) from our previous investigation, the most prevelant microorganisms were Mycoplasma pneumonia (26%) and Influenza-B (19.8%). Coinfections were reported in 58% of samples and the most common association was found between B. pertussis and Adenovirus (12.2%). CONCLUSIONS: There was a high prevalence of Adenovirus, Mycoplasma pneumoniae and other etiologies in patients with a probable diagnosis of pertussis. Despite the presence of persistent cough lasting at least two weeks and other clinical characteristics highly suspicious of pertussis, secondary etiologies should be considered in children under 5 years-old in order to give a proper treatment.

A Population-Based Study of Recurrent Symptomatic Bordetella pertussis Infections in Children in California, 2010-2015.

BACKGROUND: Natural infection with Bordetella pertussis is thought to result in 4-20 years of immunity against subsequent symptomatic pertussis infection. However, these estimates are based on studies in unvaccinated or whole-cell pertussis-vaccinated children. We conducted a population-based study of pertussis infection and reinfection during a 5-year period in California in an cohort vaccinated exclusively with acellular pertussis (aP) vaccine. METHODS: California surveillance data were reviewed to identify all children with 2 reported incidents of pertussis with symptom onset between 1 January 2010 and 31 December 2015. Case investigation reports were reviewed, and children with ≥2 episodes of symptomatic pertussis infection that met the case definition were included. RESULTS: Of 26259 pertussis cases reported in children (aged <18 years), 27 children met the inclusion criteria. Recurrent cases occurred among children of all ages; 5 (19%) were <6 months of age at the time of their first illness. The time from initial infection to reinfection was <1 year in 11 (41%) cases. Twenty-one children (78%) had received ≥3 doses of diphtheria and tetanus toxoids and aP vaccine at the time of their first pertussis infection, 1 (4%) had received 1 dose, and 5 (19%) were unvaccinated. CONCLUSIONS: Recurrent cases of pertussis infection are extremely rare. Based on this surveillance data, approximately 0.1% of children who were infected with pertussis experienced a clinically significant second episode of pertussis within 4 years. More research is needed to understand the immune response to B. pertussis infection in children vaccinated with aP vaccines.

Identifying Children at Risk of Malignant Bordetella pertussis Infection.

OBJECTIVE: To identify factors associated with malignant pertussis. DESIGN: A retrospective case notes review from January 2003 to August 2013. Area under the receiver-operator characteristic curve was used to determine how well vital sign and white cell characteristics within 48 hours of hospital presentation identified children with malignant pertussis. SETTING: The national children's hospital in Auckland, New Zealand. PATIENTS: One hundred fifty-two children with pertussis. MEASUREMENTS AND MAIN RESULTS: There were 152 children with confirmed pertussis identified, including 11 children with malignant pertussis. The area under the receiver-operator characteristic curve was 0.88 (95% CI, 0.78-0.97) for maximum heart rate. The optimal cut-point was 180 beats/min, which predicted malignant pertussis with a sensitivity of 73% and a specificity of 91%. The area under the receiver-operator characteristic curve was 0.92 (95% CI, 0.81-1.0) for absolute neutrophil count, 0.85 (95% CI, 0.71-0.99) for total WBC count, 0.80 (95% CI, 0.63-0.96) for neutrophil-to-lymphocyte ratio, and 0.77 (95% CI, 0.58-0.92) for absolute lymphocyte count. All children with malignant pertussis had one or more of heart rate greater than 180 beats/min, total WBC count greater than 25 × 10/L, and neutrophil-to-lymphocyte ratio greater than 1.0 with an area under the receiver-operator characteristic curve of 0.96 (95% CI, 0.91-1.0) for a multivariate model that included these three variables. CONCLUSIONS: Clinical predictors of malignant pertussis are identifiable within 48 hours of hospital presentation. Early recognition of children at risk of malignant pertussis may facilitate early referral to a PICU for advanced life support and selection for trials of investigational therapies.

Paediatric Active Enhanced Disease Surveillance (PAEDS) annual report 2015: Prospective hospital-based surveillance for serious paediatric conditions.

INTRODUCTION: The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine preventable diseases and potential adverse events following immunisation (AEFI). PAEDS data is used to better understand these conditions, inform policy and practice under the National Immunisation Program, and enable rapid public health responses for certain conditions of public health importance. PAEDS enhances data available from other Australian surveillance systems by providing prospective, detailed clinical and laboratory information on children with selected conditions. This is the second of the planned annual PAEDS reporting series, and presents surveillance data for 2015. METHODS: Specialist surveillance nurses screened hospital admissions, emergency department records, laboratory and other data, on a daily basis in 5 paediatric tertiary referral hospitals in New South Wales, Victoria, South Australia, Western Australia and Queensland to identify children with the selected conditions. Standardised protocols and case definitions were used across all sites. Conditions under surveillance in 2015 included acute flaccid paralysis (a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis and varicella-zoster virus infection (varicella and herpes zoster). Most protocols restrict eligibility to hospitalisations, ED only presentations are also included for some conditions. METHODS: : In 2015, there were 674 cases identified across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach WHO reporting targets; identification of signals for Mycoplasma pneumoniae and parechovirus-related outbreaks (ACE surveillance); and demonstration of high influenza activity with vaccine effectiveness (VE) analysis supportive of vaccination. Surveillance for IS remains ongoing with any identified AEFIs reported to the relevant State Health Department; varicella and herpes zoster case numbers decreased slightly from previous years in older children not eligible for catch-up. Pertussis case numbers increased in early 2015 and analysis of cases in children aged <1 year demonstrated the importance of timely childhood and maternal immunisation. CONCLUSIONS: PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using hospital-based sentinel surveillance.

Whooping cough in a renal transplant recipient.

Whooping cough is a respiratory infection with a severity that varies with age, immune status, and probably with other factors such as the degree of exposure and the virulence of the organism. The most frequent microorganism responsible for whooping cough is Bordetella pertussis. We present the case of a 62-year-old renal transplant recipient presenting with typical and severe manifestations of whooping cough caused by B. pertussis.

Many Inflammatory Bowel Disease Patients Are Not Immune to Measles or Pertussis.

BACKGROUND: Current guidelines emphasize vaccination for influenza and pneumococcus for IBD patients and the avoidance of live virus vaccines for those who are on immunosuppressive (ISS) therapy. Given the recent resurgence of measles and pertussis infections, we assessed the immune status of our IBD population in order to advise about these risks. METHODS: We prospectively collected measles and pertussis titers in our IBD patients from February 1-May 1, 2015. Immune status based on standard threshold values was determined: measles antibodies ≤0.8 antibody index (AI) = negative immunity, 0.9-1.1 AI = equivocal immunity and titers ≥1.2 AI = positive immunity. For pertussis immunity, anti-pertussis antibodies ≤5 IU/mL were considered negative immunity. Univariate analysis was performed to examine predictive factors including age, disease duration, and current medical therapies. RESULTS: A total of 122 patients' titers were assessed (77 Crohn's disease, 1 indeterminate colitis, and 45 ulcerative colitis). Sixteen (13.1 %) patients lacked detectable immunity to measles, and four (3 %) had equivocal immunity. Twelve (75 %) of the measles non-immune patients were on ISS therapy versus 65 (64 %) of 102 immune patients (OR 1.7, 95 % CI 0.5-5.9, p = 0.34). Out of 96 patients, 58 (60 %) were not immune to pertussis. Disease duration ≥10 years and age ≥50 were associated with significant lower measles titers. CONCLUSIONS: A significant number of our IBD patients lack immunity to measles, and a majority of our IBD patients do not have detectable immunity to pertussis. Importantly, the majority of the measles non-immune patients are on ISS therapy and therefore unable to receive a booster.

Severe immune thrombocytopenia following diphtheria, tetanus, pertussis and polio vaccination in a 36-year-old Caucasian woman: a case report.

BACKGROUND: Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet counts and increased bleeding risk. The disease may be induced by other disorders, including malignancies, autoimmune diseases, infectious agents or drugs. However, ITP has also been described following vaccinations, such as the measles-mumps-rubella vaccination. In rare cases, ITP may occur in children who received a DTaP-IP (diphtheria, tetanus, acellular pertussis vaccine and inactivated poliovirus) vaccine. Hereinafter, we report the first well-documented cases of ITP in an adult patient in the temporal context of a DTaP-IP vaccination. CASE PRESENTATION: This case report attempts to capture the life-threatening picture of a 36-year-old otherwise healthy Caucasian woman with newly diagnosed severe immune thrombocytopenia in the temporal context of a DTaP-IP vaccination. Four days after receiving the vaccine, the women presented to her primary care physician with malaise, fever and recurrent epistaxis. Clinical examination revealed oral petechiae, ecchymoses, and non-palpable petechiae on both legs. The patient was immediately referred to a local hematology unit where she developed hematuria and an intestinal bleeding (WHO Bleeding Grade III) requiring multiple transfusions. After receiving oral corticosteroids and intravenous immunoglobulins, her platelets gradually recovered. Common causes of secondary ITP were ruled out by laboratory investigations, bone marrow and peripheral blood examinations. This raises the possibility of a (secondary) vaccination-associated thrombocytopenia. To the best of our knowledge, this is the first well-documented case of a DTaP-IP vaccination-related ITP in an adult patient in the English literature. CONCLUSION: Although a causal connection between both entities may not be established, we would like to raise awareness in clinicians that ITP following DTaP-IP vaccinations is potentially not limited to children, but may also occur in adults. Users of DTaP-IP booster vaccines should be alert of the possibility of such adverse reactions.

Association of Diphtheria-Tetanus-Acellular Pertussis Vaccine Timeliness and Number of Doses With Age-Specific Pertussis Risk in Infants and Young Children.

Importance: In most countries, the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is administered as a 3-dose infant series followed by additional booster doses in the first 5 years of life. Short-term immunity from the DTaP vaccine can depend on the number, timing, and interval between doses. Not receiving doses in a timely manner might be associated with a higher pertussis risk. Objective: To examine the association between number and timeliness of vaccine doses and age-specific pertussis risk. Design, Setting, and Participants: This population-based, retrospective cohort study used Washington State Immunization Information System data and pertussis surveillance data from Public Health Seattle and King County, Washington. Included participants were children aged 3 months to 9 years born or living in King County, Washington, between January 1, 2008, and December 31, 2017. Data were analyzed from June 30 to December 1, 2019. Exposures: Being undervaccinated (receiving fewer than recommended doses at a given age) or delayed vaccination (not receiving doses within time frames recommended by Centers for Disease Control and Prevention). Main Outcomes and Measures: Suspected, probable, and confirmed pertussis diagnosis. Results: A total of 316 404 children (median age, 65.2 months [interquartile range, 35.3-94.1 months]; 162 025 boys [51.2%]) as of December 31, 2017, with 17.4 million person-months of follow-up were included in the analysis. A total of 19 943 children (6.3%) had no vaccines recorded in the Immunization Information System, 116 193 (36.7%) received a vaccine with a delay, and 180 268 (56.9%) were fully vaccinated with no delay. Delayed vaccination and undervaccination rates were higher for older children (17.6% delayed or undervaccinated at age 2 months for dose 1 at 3 months vs 41.6% at age 5 years for dose 5) but improved for successive birth cohorts (52.2% for 2008 birth cohort vs 32.3% for 2017 birth cohort). Undervaccination was significantly associated with higher risk of pertussis for the 3-dose primary series (adjusted relative risk [aRR], 4.8; 95% CI, 3.1-7.6), the first booster (aRR, 3.2; 95% CI, 2.3-4.5), and the second booster (aRR, 4.6; 95% CI, 2.6-8.2). However, delay in vaccination among children who received the recommended number of vaccine doses was not associated with pertussis risk. Conclusions and Relevance: The results of this cohort study suggest that undervaccination is associated with higher pertussis risk. Short delays in vaccine receipt may be less important if the age-appropriate number of doses is administered, but delaying doses is not recommended. Ensuring that children receive all doses of pertussis vaccine, even if there is some delay, is important.

IL-17 mediates protective immunity against nasal infection with Bordetella pertussis by mobilizing neutrophils, especially Siglec-F+ neutrophils.

Understanding the mechanism of protective immunity in the nasal mucosae is central to the design of more effective vaccines that prevent nasal infection and transmission of Bordetella pertussis. We found significant infiltration of IL-17-secreting CD4+ tissue-resident memory T (TRM) cells and Siglec-F+ neutrophils into the nasal tissue during primary infection with B. pertussis. Il17A-/- mice had significantly higher bacterial load in the nasal mucosae, associated with significantly reduced infiltration of Siglec-F+ neutrophils. Re-infected convalescent mice rapidly cleared B. pertussis from the nasal cavity and this was associated with local expansion of IL-17-producing CD4+ TRM cells. Depletion of CD4 T cells from the nasal tissue during primary infection or after re-challenge of convalescent mice significantly delayed clearance of bacteria from the nasal mucosae. Protection was lost in Il17A-/- mice and this was associated with significantly less infiltration of Siglec-F+ neutrophils and antimicrobial peptide (AMP) production. Finally, depletion of neutrophils reduced the clearance of B. pertussis following re-challenge of convalescent mice. Our findings demonstrate that IL-17 plays a critical role in natural and acquired immunity to B. pertussis in the nasal mucosae and this effect is mediated by mobilizing neutrophils, especially Siglec-F+ neutrophils, which have high neutrophil extracellular trap (NET) activity.

Association of Pertussis Toxin with Severe Pertussis Disease.

Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, both local and systemic. Predominant among these toxins is pertussis toxin (PT), a multi-subunit protein toxin that inhibits signaling through a subset of G protein-coupled receptors in mammalian cells. PT activity has been linked with severe and lethal pertussis disease in young infants and a detoxified version of PT is a common component of all licensed acellular pertussis vaccines. The role of PT in typical pertussis disease in other individuals is less clear, but significant evidence supporting its contribution to pathogenesis has been accumulated from animal model studies. In this review we discuss the evidence indicating a role for PT in pertussis disease, focusing on its contribution to severe pertussis in infants, modulation of immune and inflammatory responses to infection, and the characteristic paroxysmal cough of pertussis.

Estandarización de un ELISA para la cuantificación de anticuerpos IgG humanos contra células enteras de Bordetella pertussis / Standardization of an ELISA for the quantification of human IgG antibodies against whole cells of Bordetella pertussis

Bordetella pertussis es un patógeno exclusivo de humanos que causa la tos ferina, enfermedad respiratoria aguda que afecta principalmente a la población pediátrica. Existen dos tipos de vacunas comercializadas contra este patógeno: celulares y acelulares. Las vacunas celulares han sido extensamente utilizadas y siguen teniendo gran relevancia. El presente trabajo tuvo como objetivo la estandarización de un ELISA para la cuantificación de anticuerpos IgG contra células enteras de Bordetella pertussis. Para ello se determinó la concentración de recubrimiento, el rango lineal de la curva, los parámetros de precisión intra e interensayo, la especificidad, el valor de corte y el límite de detección. Se determinó como concentración de recubrimiento 0,5 UO/mL de células enteras. La curva estándar utilizando un suero de referencia internacional presentó un buen ajuste a una función polinómica en un intervalo entre las diluciones 1/100 y 1/24.300 con un coeficiente de correlación R2≥0,98. Los coeficientes de variación en los ensayos de precisión intra e interensayo estuvieron en los intervalos establecidos para cada uno (≤10 por ciento, ≤20 por ciento respectivamente). Los resultados obtenidos avalan el empleo de este ELISA cuantitativo para la evaluación de la respuesta a células enteras de Bordetella pertussis en ensayos clínicos(AU)

Bordetella pertussis is a pathogen exclusive to humans that causes pertussis, an acute respiratory disease that mainly affects the pediatric population. There are two types of vaccines commercially available against this pathogen: cellular and acellular. Cellular vaccines have been widely used and continue to be of great relevance. The aim of the present work was to standardize an ELISA for the quantification of IgG antibodies against whole cells of Bordetella pertussis. For this purpose, the coating concentration, the linear range of the curve, the intra- and inter-assay precision parameters, the specificity, the cut-off value and the detection limit were determined. The coating concentration was determined as 0.5 UO/mL of whole cells. The standard curve using an international reference serum presented a good fit to a polynomial function in a range between dilutions 1/100 and 1/24,300 with a correlation coefficient R2≥0.98. The coefficients of variation in the intra- and inter-assay precision tests were in the intervals established for each (≤10percent, ≤20percent respectively). The results obtained support the use of this quantitative ELISA for the evaluation of whole-cell response to Bordetella pertussis in clinical trials(AU)

Risk Markers for Pertussis Among Infants <4 Months of Age: Understanding the Hispanic Disparity.

OBJECTIVES: Hispanic infants are at greater risk of pertussis compared with other racial/ethnic groups. Studies have shown that the source of Bordetella pertussis infection for most infants is household members. Using a case-control study, we examined risk markers for pertussis among Hispanic and non-Hispanic infants and evaluated whether maternal parity, a proxy for household size, contributes to the ethnic disparity. METHODS: We evaluated infants born in California during 2013-2014; cases were infants reported to California Department of Public Health with pertussis occurring before 4 months of age, and controls were infants who survived to at least 4 months of age without pertussis. Bivariate comparisons and multivariate logistic regression models were used to identify risk markers for pertussis in Hispanic and non-Hispanic infants. RESULTS: Increased maternal parity was associated with greater risk of pertussis, with a clear dose response observed with increasing risk for additional prior births. Teenage mothers were more likely to have infants with pertussis. These were both independent risk factors across all racial/ethnic groups, even when adjusting for important covariates. Preterm birth and Medicaid insurance were also identified as independent risk markers among Hispanic infants only. CONCLUSIONS: Infants of all races/ethnicities with older siblings or born to younger mothers are at increased risk of pertussis. Among Hispanic infants, prematurity and Medicaid insurance were independent risk markers for pertussis. These factors highlight the need to ensure prompt immunization of pregnant women with Tdap at the earliest opportunity starting at 27 weeks gestation.

Bordetella pertussis infections in travelers: data from the GeoSentinel global network.

Background: Pertussis is a highly contagious, vaccine-preventable respiratory infection that is endemic worldwide. There are limited data regarding the occurrence of pertussis in travelers. The objective of this study is to identify travel-related pertussis cases reported to the GeoSentinel Surveillance Network. Methods: This is a descriptive, retrospective analysis of GeoSentinel records from 25 travel/tropical medicine clinics in 16 countries. Frequencies of demographic and travel-related characteristics and symptoms of 74 cases of pertussis in travelers and new immigrants from 1999 to 2015 were analysed. Results: There were 74 probable and confirmed cases of pertussis in the GeoSentinel database; median age was 44 years, and 38 (51%) patients were female. Tourism was the most common reason for travel (41; 55%). Country of exposure was determined in 66 cases with travelers returning from India and China constituting the highest number of cases (10 cases each; 15% each). Seventy of 74 (95%) patients had respiratory symptoms, while fatigue and fever were reported by 21 (28%) and 20 (27%), respectively. Immunization status against pertussis was unknown. Most cases were reported after 2005 (69; 93%). Conclusions: Our study describes 74 cases of pertussis acquired during travel and reported to the GeoSentinel Network. Pertussis should be considered in returned travelers who present with respiratory symptoms. Surveillance and detection of imported cases are important to prevent onward transmission in the community. The pre-travel consultation provides an opportunity to verify immunization status and provide routine vaccinations such as pertussis.

A Ten-Year Case-Control Study of Passive Smoke Exposure as a Risk Factor for Pertussis in Children.

The authors conducted a matched case-control study of laboratory-confirmed pertussis cases, occurring from 1/1/1996 to 12/31/2005, in children up to 12 years of age who were members of a large managed care organization. Sixty-five laboratoryconfirmed cases of pertussis were identified. Using multivariable conditional logistic regression analysis, the authors did not detect a statistically significant association between pertussis and household passive exposure to cigarette smoking.

Pertussis.

Pertussis as an infectious disease exhibits a number of unusual features, both with respect to its epidemiology and to the interaction of the bacteia with the infected host. Evidence that a virus may in some cases be the etiology of the syndrome has been reviewed and seems to be have been established in certain instances. Pertussis caused by a virus would not be difficult to accept insofar as the respiratory manifestations of the disease are concerned. It is difficult, however, to reconcile the hematologic changes of pertussis with what is presently known about the usual virus infection of humans. The clinical syndrome itself is suficiently unique as to be recognized in most cases. The use of antibiotics has considerably reduced the mortality of the disease by allowing treatment of complications. The other serious complication of disease, pertussis encephalopathy, remains a problem. The possible occurrence of hypoglycemia during pertussis has been noted and deserves further documentation especially in that it may contribute to the encephalopathy...

Etiology of pertussis syndrome.

One hundred patients with clinical pertussis were studied to determine the etiology of pertussis syndrome. Forty-two (42%) of the patients had either Bordetella pertussis of Bordetella parapertussis isolated from the nasopharynx. In additional 36 (36%) patients, B pertussis was isolated from the nasopharynx of the associated index case or family contact case. Thus, Bordetella was isolated from 78 (78%) of the patients or from their immediate family group. Of the 22 culture-negative patients residing in culture-negative families, 12 had serologic evidence of Bordetella infection and another was from a family group in which two members were seropositive. Therefore, 91 patients (91%) had bacteriologic or serologic evidence of Bordetella infection themselves or within their families. Viral cultures were obtained on 75 of the patients. Adenoviruses were isolated from 33% of those with positive cultures for B pertussis and from 14% of those with negative cultures. In the group without direct or indirect, bacteriologic or serologic evidence of Bordetella infection, the adenoviral isolation rate (13%) was not significantly different from the adenoviral isolation rate (33%) in patients with a positive bacterial culture. These data do not support a role of adenovirus alone in causing pertussis syndrome.

The role of antibiotics, immunizations, and adenoviruses in pertussis.

Sixty-five patients with pertussis were identified by a clinical criterion, and Bordetella pertussis was isolated from 75% of these patients or their symptomatic household contacts. Negative nasopharyngeal cultures were usually associated with either a history of antibiotic therapy with erythromycin or tetracycline (two of three patients), two or more diphtheria and tetanus toxoids with pertussis (DTP) vaccines (six of eight patients), or both (two of three patients). Erythromycin therapy resulted in the elimination of B. pertussis from the nasopharynx in 2 to 7 days (mean, 3.6 days) compared with 7 to 17 or more days (mean, greater than 12 days) in patients treated with no antibiotics, but had no effect on the duration or severity of illness as judged by length of hospitalization. Adenoviruses were recovered from five of 44 patients cultured. Four of these isolates were from throat swabs obtained early in the illness and the remaining isolate was from one of 33 repeated viral cultures obtained two to three weeks later; B. pertussis was also isolated from these five patients. Paired serum samples were obtained from only two of these patients. Neither demonstrated a fourfold rise in adenoviral complement-fixing antibodies. Therefore, in these patients, adenoviral isolation may have been secondary to reactivation of a latent viral infection by infection with B. pertussis.