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1.
Trop Doct ; 51(1): 99-102, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32811337

ABSTRACT

Neonatal pertussis is a resurging disease, possibly due to waning immunity in pregnant women. We report seven cases of neonatal pertussis (Bordetella pertussis DNA PCR positive) in this retrospective study conducted at a tertiary care teaching hospital in north India over eight months (March to October 2018). All except one were male infants and presented at the age of 14-30 days with paroxysmal cough in all, four had fever, four had respiratory distress, three had similar illness in the family, and two had leucocytosis. All recovered well with azithromycin. The duration of hospital stay was 5-7 days. A strong suspicion of neonatal pertussis in neonates with paroxysmal cough and similar family history should be maintained as the prognosis is excellent, if treated appropriately.


Subject(s)
Whooping Cough/diagnosis , Whooping Cough/drug therapy , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Bordetella pertussis/isolation & purification , Female , Hospitals, Teaching , Humans , India , Infant, Newborn , Length of Stay , Male , Prognosis , Retrospective Studies , Treatment Outcome , Whooping Cough/physiopathology
2.
J Prev Med Hyg ; 61(1): E66-E75, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32490271

ABSTRACT

INTRODUCTION: The present study aims to characterize knowledge, attitudes and practices in a sample of occupational physicians (OPh) towards pertussis immunization in healthcare workers (HCWs) from pediatric settings. MATERIAL AND METHODS: A total of 148 OPh (45.9% males, mean age of 40.3 ± 13.2 years) compiled a web questionnaire including a knowledge test on Italian recommendations for HCWs, epidemiology and pathology of pertussis infection, being then investigated about risk perceptions and vaccination practices. A General Knowledge Score (GKS) and a Risk Perception Score (RPS) were calculated. Multivariate odds ratios (OR) for predictors of vaccine propensity were calculated through regression analysis. RESULTS: 78 participants regularly recalled pertussis vaccination status and/or performed pertussis vaccination in HCWs (52.7%). Proactive status was correlated with the aim to avoid pertussis infection in HCWs and its diffusion to other adults (p < 0.001, both statements). GKS was satisfying (72.4% ± 14.9), but participants underestimated the clinical issues of pertussis infection (RPS 60.8% ± 9.5) when confronted with influenza (73.9% ± 10.9) and HBV infection (68.1% ± 10.1). GKS and RPS were well correlated (r = 0.244, p = 0.003). Eventually, a better GKS and the aim to avoid pertussis infection in HCWs were predictive of a proactive status for pertussis vaccination (OR 4.186 95%CI 1.809-9.685 and OR 11.459, 95%CI 3.312-39.651, respectively). CONCLUSIONS: Adherence of OPh to HCWs pertussis vaccination was unsatisfying. As knowledge status was predictive for vaccine propensity, information programs for OPh should be more appropriately designed, stressing that HCWs may represent a significant reservoir for pertussis infection in high risk groups (e.g. children/newborns, frail elderly).


Subject(s)
Attitude of Health Personnel , Clinical Competence , Health Personnel , Occupational Medicine , Pertussis Vaccine/therapeutic use , Whooping Cough/prevention & control , Adult , Female , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Pediatrics , Practice Patterns, Physicians' , Whooping Cough/epidemiology , Whooping Cough/physiopathology
3.
Clin Lab ; 66(6)2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32538045

ABSTRACT

BACKGROUND: Pertussis, caused by Bordetella pertussis (B. pertussis), is a highly transmissible, acute respiratory disease that occurs in many countries. Diagnosis of pertussis continues to be a challenge using traditional tests due to their turn-around time and sensitivity. Herein, we rapidly and accurately screened a family cluster of pertussis from a child and her mother. METHODS: We used an automated nested multiplex PCR system which included B. pertussis, influenza A virus, and 19 other respiratory pathogens. RESULTS: We detected B. pertussis, influenza A virus H1-2009 (FluA-2009), adenovirus, and respiratory syncytial virus (RSV) in the child, and the mother of the child was positive for B. pertussis and FluA-2009. CONCLUSIONS: Active and timely screening for pertussis of adult family members should be considered. The detection of multiple respiratory pathogens may guide effective antibiotic therapies. This could be a novel test for the prevention of pertussis.


Subject(s)
Adenoviridae/isolation & purification , Anti-Bacterial Agents , Antiviral Agents/administration & dosage , Bordetella pertussis/isolation & purification , Influenza A virus/isolation & purification , Multiplex Polymerase Chain Reaction/methods , Respiratory Syncytial Viruses/isolation & purification , Whooping Cough , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/classification , Coinfection/diagnosis , Coinfection/microbiology , Coinfection/physiopathology , Coinfection/therapy , Disease Hotspot , Family Health , Female , Hospitalization , Humans , Infant , Microbiological Techniques/methods , Severity of Illness Index , Whooping Cough/diagnosis , Whooping Cough/microbiology , Whooping Cough/physiopathology , Whooping Cough/therapy
4.
Clin Pediatr (Phila) ; 59(7): 641-646, 2020 06.
Article in English | MEDLINE | ID: mdl-32075427

ABSTRACT

Objectives. To identify risk factors associated with the prognosis of pertussis-like coughing. Methods. A retrospective study on children hospitalized with pertussis-like coughing from 2018 to 2019. We collected all the case data from medical records including age, gender, vaccination, clinical symptoms, complication, pathogens, white blood cell (WBC) count, lymphocyte ratio, application of macrolide antibiotics, usage of sulfamethoxazole, and usage of inhaled glucocorticoids. Logistic regression was used in this study. Results. A total of 213 hospitalized children with pertussis-like coughing were included in this study. About 70 children were cured within 2 weeks. One120 children were cured from 2 weeks to 3 months, including cases of initial attack and relapse. Symptoms lasting longer than 3 months accounts for 10.8%. Bordetella pertussis, WBC count >20 × 109/L and lymphocyte ratio >60% were associated with poor prognosis (P < .05). Conclusions. Bordetella pertussis, WBC count, and lymphocyte ratio are independent risk factors for poor prognosis.


Subject(s)
Cough/etiology , Whooping Cough/complications , Whooping Cough/physiopathology , Age Factors , Anti-Bacterial Agents/therapeutic use , Child, Preschool , Cough/physiopathology , Female , Glucocorticoids/therapeutic use , Humans , Infant , Infant, Newborn , Leukocyte Count/statistics & numerical data , Lymphocyte Count/statistics & numerical data , Male , Retrospective Studies , Risk Factors , Sex Factors , Vaccination/statistics & numerical data , Whooping Cough/drug therapy
6.
Infect Immun ; 87(10)2019 10.
Article in English | MEDLINE | ID: mdl-31308086

ABSTRACT

As important players in the host defense system, commensal microbes and the microbiota influence multiple aspects of host physiology. Bordetella pertussis infection is highly contagious among humans. However, the roles of the microbiota in B. pertussis pathogenesis are poorly understood. Here, we show that antibiotic-mediated depletion of the microbiota results in increased susceptibility to B. pertussis infection during the early stage. The increased susceptibility was associated with a marked impairment of the systemic IgG, IgG2a, and IgG1 antibody responses to B. pertussis infection after antibiotic treatment. Furthermore, the microbiota impacted the short-lived plasma cell responses as well as the recall responses of memory B cells to B. pertussis infection. Finally, we found that the dysbiosis caused by antibiotic treatment affects CD4+ T cell generation and PD-1 expression on CD4+ T cells and thereby perturbs plasma cell differentiation. Our results have revealed the importance of commensal microbes in modulating host immune responses to B. pertussis infection and support the possibility of controlling the severity of B. pertussis infection in humans by manipulating the microbiota.


Subject(s)
Bordetella pertussis/immunology , Dysbiosis/immunology , Gastrointestinal Microbiome/immunology , Immunity, Humoral , Symbiosis/immunology , Whooping Cough/immunology , Ampicillin/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Antibodies, Bacterial/biosynthesis , Antibodies, Bacterial/classification , Bacteroidetes/classification , Bacteroidetes/drug effects , Bacteroidetes/growth & development , Bacteroidetes/immunology , Bordetella pertussis/growth & development , Bordetella pertussis/pathogenicity , Dysbiosis/microbiology , Dysbiosis/physiopathology , Female , Firmicutes/classification , Firmicutes/drug effects , Firmicutes/growth & development , Firmicutes/immunology , Gastrointestinal Microbiome/drug effects , Immunity, Innate , Immunoglobulin G/biosynthesis , Immunoglobulin G/classification , Metronidazole/pharmacology , Mice , Mice, Inbred BALB C , Neomycin/pharmacology , Proteobacteria/classification , Proteobacteria/drug effects , Proteobacteria/growth & development , Proteobacteria/immunology , Symbiosis/drug effects , Vancomycin/pharmacology , Whooping Cough/microbiology , Whooping Cough/physiopathology
8.
Expert Rev Vaccines ; 18(3): 205-208, 2019 03.
Article in English | MEDLINE | ID: mdl-30736722

ABSTRACT

INTRODUCTION: Today, in the developed world, virtually all deaths due to Bordetella pertussis illnesses occur in young infants. Areas Covered: Pertussis in young infants is characterized by an afebrile cough illness with coryza, apnea, seizures, cyanosis, and emesis. Severe illness is associated with high leukocyte and lymphocyte counts, rapid respiratory and cardiac rates and pneumonia. Many routine intensive care treatment procedures are detrimental: these include steroids and nitric oxide. Preventative measures include: quarantine, prophylactic antimicrobial agents and immunizations of the mother to be with Tdap between 27 and 36 weeks gestation. Expert Opinion: Infants deaths are due to the irreversible pulmonary hypertension which is caused by aggregates of leukocytes in the small vessels in the lung. The leukocytosis with lymphocytosis is due to pertussis toxin. It can be treated by exchange blood transfusions. However for this to be successful it needs to be started before shock or organ failure has occurred. To prevent pertussis in young infants, attention needs to be directed to the diagnosis and treatment of pertussis in adolescents and adults. Also important are antimicrobial prophylaxis in the infant and the immunization of mothers to be with Tdap vaccine during all pregnancies.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Vaccination/methods , Whooping Cough/prevention & control , Adolescent , Adult , Bordetella pertussis/isolation & purification , Female , Humans , Infant , Pregnancy , Whooping Cough/mortality , Whooping Cough/physiopathology
11.
Altern Ther Health Med ; 24(2): 58-61, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28987075

ABSTRACT

Context • Pertussis cough (whooping cough) is distressing due to the intensity and chronicity of its cough. No specific drugs are available that can alleviate the cough's intensity or significantly shorten its duration. Homeopathic medicines are used for a wide variety of medical conditions, including cough. Objective • The study investigated the benefits of homeopathic medicines for whooping cough, to alleviate the cough's intensity and to shorten its duration. Design • The current study was a case series of patients with whooping cough. Setting • The study took place at one of the suburban hospital clinics of the Ann & Robert H. Lurie Children's Hospital of Chicago (Chicago, IL, USA). Participants • Participants were 20 patients aged 21 mo to 20 y, of whom 11 were female and 18 were male, who visited the hospital clinic for treatment of the chronic cough that is characteristic of whooping cough. The details of the cases of 3 representative participants are highlighted in the text. Intervention • The 3 representative patients all received 1 dose weekly of a 30c dilution of homeopathic pertussinum and a 6c dilution of homeopathic Drosera 3 times daily. The homeopathic medicines most often used for the other participants were the same doses of pertussinum and Drosera. Outcome Measures • Verbal feedback from patient or family were obtained at the follow-up visits. Results • The intensity and duration of participant's coughs were alleviated within days to 1 wk in most cases. Conclusions • Homeopathic medicines can alleviate the intensity or reduce the duration of whooping cough, with no adverse effects.


Subject(s)
Materia Medica/therapeutic use , Whooping Cough/drug therapy , Whooping Cough/physiopathology , Adolescent , Adult , Chicago , Child , Child, Preschool , Drosera , Female , Humans , Infant , Male , Materia Medica/administration & dosage , Young Adult
12.
Clin Infect Dis ; 65(5): 811-818, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-29017283

ABSTRACT

BACKGROUND: In 2012, >48000 pertussis cases were reported in the United States. Many cases occurred in vaccinated persons, showing that pertussis vaccination does not prevent all pertussis cases. However, pertussis vaccination may have an impact on disease severity. METHODS: We analyzed data on probable and confirmed pertussis cases reported through Enhanced Pertussis Surveillance (Emerging Infections Program Network) between 2010 and 2012. Surveillance data were collected through physician and patient interview and vaccine registries. We assessed whether having received an age-appropriate number of pertussis vaccines (AAV) (for persons aged ≥3 months) was associated with reduced odds of posttussive vomiting, a marker of more clinically significant illness, or of severe pertussis (seizure, encephalopathy, pneumonia, and/or hospitalization). Adjusted odds ratios were calculated using multivariable logistic regression. RESULTS: Among 9801 pertussis patients aged ≥3 months, 77.6% were AAV. AAV status was associated with a 60% reduction in odds of severe disease in children aged 7 months-6 years in multivariable logistic regression and a 30% reduction in odds of posttussive vomiting in persons aged 19 months-64 years. CONCLUSIONS: Serious pertussis symptoms and complications are less common among AAV pertussis patients, demonstrating that the positive impact of pertussis vaccination extends beyond decreasing risk of disease.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines , Vaccination/statistics & numerical data , Whooping Cough , Adolescent , Child , Child, Preschool , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Diphtheria-Tetanus-acellular Pertussis Vaccines/therapeutic use , Female , Humans , Infant , Male , Odds Ratio , Retrospective Studies , Severity of Illness Index , United States , Whooping Cough/epidemiology , Whooping Cough/physiopathology , Whooping Cough/prevention & control
13.
J Infect ; 75(5): 426-432, 2017 11.
Article in English | MEDLINE | ID: mdl-28867343

ABSTRACT

OBJECTIVES: We assessed the value of the clinical symptoms included in the case definition of pertussis in household contacts of laboratory-confirmed cases. METHODS: A prospective epidemiological study was made in two Spanish regions. Household contacts were identified for each confirmed case reported during 2012 and 2013. Two clinical samples were taken to determine the presence or absence of Bordetella pertussis by culture or real-time PCR. Clinical variables, age and vaccination status were recorded. Positive and negative likelihood ratios (PLR, NLR) were estimated for each symptom. RESULTS: 2852 household contacts of 688 confirmed cases were reported. 178 household contacts with clinical symptoms were analyzed: 150 were laboratory confirmed and 28 were not. The clinical symptom with the highest PLR in comparison with the NLR was paroxysmal cough(PLR 4.76; 95% CI 1.91-11.87 and NLR 0.37; 95% CI 0.28-0.49). The contrast between the PLR and NLR was especially important for persons aged <18 years (PLR 7.08; 95% CI 1.10-45.74 and NLR 0.32; 95% CI 0.21-0.49). CONCLUSIONS: The clinical symptoms of pertussis are poor predictors of pertussis disease, independently of the vaccination status. Differences were observed between persons aged <18 years and adults. To adopt the appropriate treatment and control measures, rapid laboratory confirmation by PCR of all household contacts of confirmed cases who present any clinical symptoms compatible with pertussis should be recommended.


Subject(s)
Whooping Cough/physiopathology , Adolescent , Adult , Age Factors , Bordetella pertussis/isolation & purification , Child , Child, Preschool , Cough/diagnosis , Family Health , Female , Humans , Infant , Likelihood Functions , Male , Spain/epidemiology , Whooping Cough/diagnosis , Whooping Cough/epidemiology , Whooping Cough/transmission , Young Adult
14.
J Paediatr Child Health ; 53(3): 257-262, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28058755

ABSTRACT

AIM: To describe children with pertussis who required intensive care. METHODS: This is a retrospective analysis of pertussis admissions to all (six) national intensive care units in Greece from 2003 to 2013. RESULTS: A total of 31 children were included, 28 of whom were younger than 12 months old. Cough was the most prominent symptom, being present in 27 of 31 (87%) patients, and on admission, only 7 (22.6%) satisfied the case definition. Mechanical ventilation was initiated in 13 (42%) patients. Six patients died because of respiratory failure (two) or multi-organ system failure (four). The patients who died had significantly higher white blood cell counts (WBC) (77 800-31 600, P = 0.031) and neutrophils (29 016-12 795, P = 0021) than those who survived and lower minimum values of serum sodium (125-133, P = 0002). They also had a longer duration of hospitalisation prior to their paediatric intensive care unit admission (6-1 days, P = 0022). Three patients were diagnosed with pulmonary hypertension, and only one of them survived. Age, gender and immunisation status did not differ between survivors and non-survivors. Two patients received exchange blood transfusion, and survival benefit was not apparent. CONCLUSION: Young infants are at risk of severe pertussis, resulting in serious complications or death. Elevated WBC and low serum sodium are associated with higher mortality. Despite advances in life support and treatment of organ failure in childhood critical illness, pertussis still has substantial mortality.


Subject(s)
Bordetella pertussis/isolation & purification , Intensive Care Units, Pediatric , Whooping Cough/physiopathology , Critical Care/methods , Female , Greece/epidemiology , Humans , Infant , Male , Medical Audit , Retrospective Studies , Whooping Cough/diagnosis , Whooping Cough/epidemiology
15.
Acta Clin Belg ; 71(2): 86-91, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27075799

ABSTRACT

OBJECTIVE: Report on the pitfalls of serodiagnosis of pertussis in Belgium for 2013 by the NRC Bordetella. METHODS: Determine cases of acute infection using an anti-pertussis toxin (PT) IgG antibody ELISA. RESULTS: A total of 2471 serum samples were received. Clinical information on the duration of cough (at moment of blood sampling) is essential for a reliable interpretation of the results. In order to avoid false negative results, 213 samples for which this information was lacking were not tested. For a total of 2179 patients tested, 520 (23.9%) had antibody levels indicative of an acute infection, 261 (12%) samples were diagnosed as positive (indicative of a pertussis infection or vaccination during the last year), 143 (6.7%) samples were classified as doubtful and 752 (34,5%) (35.5%) were diagnosed as negative. The serodiagnosis of pertussis has limited value for the early diagnosis of the disease and PCR analysis on nasopharyngeal swabs is the method of choice during the first 2 weeks and always for young children <1 year old. For sera collected during the first 2 weeks with anti-PT levels below the threshold for acute infection, a second sample collected 2-3 weeks later is needed a definitive diagnosis. For 503 (23.0%) early samples, a second serum sample was requested but not provided. For 85 patients, for whom a second sample was received, 12.9% were eventually diagnosed as having an acute infection. CONCLUSION: In order to generate reliable serodiagnostic results for pertussis, serum samples should preferentially be collected 3 weeks after onset of symptoms.


Subject(s)
Immunoglobulin G/immunology , Pertussis Toxin/immunology , Serologic Tests , Whooping Cough/blood , Adolescent , Adult , Aged , Belgium , Bordetella pertussis , Child , Child, Preschool , Cough , Enzyme-Linked Immunosorbent Assay , Female , Geographic Information Systems , Humans , Immunoglobulin G/analysis , Immunoglobulin G/blood , Infant , Male , Middle Aged , Pertussis Toxin/analysis , Pertussis Toxin/blood , Pertussis Vaccine , Vaccination/statistics & numerical data , Whooping Cough/epidemiology , Whooping Cough/immunology , Whooping Cough/physiopathology , Young Adult
16.
J Infect ; 72(4): 460-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26850358

ABSTRACT

OBJECTIVE: To identify associations between nasopharyngeal Bordetella pertussis DNA load and clinical and epidemiological characteristics and evaluate DNA load prognostic value in pertussis severity. METHODS: Prospective observational multi-centre study including nasopharyngeal samples positive to pertussis DNA by real-time PCR collected from children and adult patients in more than 200 health centres of Catalonia (Spain) during 2012-2013. RESULTS: B. pertussis load was inversely correlated with age (rho = -0.32, p < 0.001), time to diagnosis (rho = -0.33, p < 0.001) and number of symptoms (rho = 0.13, p = 0.002). Median bacterial load was significantly higher in inpatients versus outpatients (4.91 vs. 2.55 log10 CFU/mL, p < 0.001), patients with complications versus those without (6.05 vs. 2.82 log10 CFU/mL, p < 0.001), disease incidence in summer and autumn versus spring and winter (3.50 vs. 2.21 log10 CFU/mL, p = 0.002), and unvaccinated-partially vaccinated patients versus vaccinated (4.20 vs. 2.76 log10 CFU/mL, p = 0.004). A logistic regression model including bacterial load and other candidate prognostic factors showed good prediction for hospital care (AUC = 0.94) although only age and unvaccinated status were found to be prognostic factors. CONCLUSIONS: We observed strong positive associations of nasopharyngeal bacterial load with severity outcomes of hospitalisation and occurrence of complications. Bacterial load and other independent variables contributed to an accurate prognostic model for hospitalisation.


Subject(s)
Bordetella pertussis/genetics , DNA, Bacterial/blood , Whooping Cough , Adolescent , Bacterial Load , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Prognosis , Prospective Studies , Real-Time Polymerase Chain Reaction , Spain/epidemiology , Whooping Cough/diagnosis , Whooping Cough/epidemiology , Whooping Cough/microbiology , Whooping Cough/physiopathology
17.
Lancet Infect Dis ; 15(12): 1480-4, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26298206

ABSTRACT

Whooping cough is a relatively new infectious disease afflicting human beings, compared with other infectious diseases, and is undergoing a resurgence despite decades of vaccination. The oldest known epidemic is thought to be the Paris outbreak of 1578. In this Historical Review, we describe three epidemics of whooping cough in Persia, which although arising roughly one century before the Paris outbreak, have not been examined in detail. A great amount of epidemiological detail was reported that not only distinguishes the various stages and complications of whooping cough, but also reveals unique immunological aspects of this disease. The first of these epidemics is the oldest recorded whooping cough epidemic. On the basis of epidemiological features, we propose that this whooping cough epidemic was the first to have taken place in Persia and might have been part of the first pandemic. This theory pushes back the date of first documented emergence of whooping cough by almost a century, which matches molecular data about its spread. Here, we discuss features of these early epidemics in relation to their initial emergence, potential origins, and spread to Europe.


Subject(s)
Disease Outbreaks , Whooping Cough/epidemiology , Whooping Cough/history , Age Factors , Bordetella pertussis/pathogenicity , Child , Child, Preschool , Female , History, 15th Century , History, 16th Century , Humans , Male , Persia/epidemiology , Whooping Cough/microbiology , Whooping Cough/physiopathology
18.
Med Monatsschr Pharm ; 38(12): 484-8, 2015 Dec.
Article in German | MEDLINE | ID: mdl-26837155

ABSTRACT

Whooping cough is a highly contagious respiratory disease which is caused predominantly by the gram-negative bacterium Bordetella pertussis. Further Bordetella species such as B. parapertussis and the recently discovered species B. holmesii are also involved in whooping cough-like diseases. Depending on age, vaccination status and distance to pre-infection with B. pertussis, whooping cough shows a wide range of symptoms. The disease occurs at any age, leaving only short time immunity. During the last 15 years, in industrialized countries the number of reported pertussis cases has been increased markedly. The reason for this observation is still unclear Macrolides such as azithromycin and clarithromycin are regarded as antibiotics of first choice. In Germany, combination vaccines containing acellular pertussis vaccines is the most important strategy of prevention. To ensure the best possible protection against pertussis, booster doses at determined times should be given after primary vaccination in infancy.


Subject(s)
Whooping Cough/therapy , Anti-Bacterial Agents/therapeutic use , Bordetella pertussis , Germany , Humans , Pertussis Vaccine , Whooping Cough/diagnosis , Whooping Cough/physiopathology , Whooping Cough/prevention & control
20.
Infect Immun ; 82(10): 4212-21, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25069981

ABSTRACT

Pertussis disease, characterized by severe and prolonged coughing episodes, can progress to a critical stage with pulmonary inflammation and death in young infants. However, there are currently no effective treatments for pertussis. We previously studied the role of pertussis toxin (PT), an important Bordetella pertussis virulence factor, in lung transcriptional responses to B. pertussis infection in mouse models. One of the genes most highly upregulated in a PT-dependent manner encodes an epithelial transporter of bicarbonate, chloride, and thiocyanate, named pendrin, that contributes to asthma pathology. In this study, we found that pendrin expression is upregulated at both gene and protein levels in the lungs of B. pertussis-infected mice. Pendrin upregulation is associated with PT production by the bacteria and with interleukin-17A (IL-17A) production by the host. B. pertussis-infected pendrin knockout (KO) mice had higher lung bacterial loads than infected pendrin-expressing mice but had significantly reduced levels of lung inflammatory pathology. However, reduced pathology did not correlate with reduced inflammatory cytokine expression. Infected pendrin KO mice had higher levels of inflammatory cytokines and chemokines than infected pendrin-expressing mice, suggesting that these inflammatory mediators are less active in the airways in the absence of pendrin. In addition, treatment of B. pertussis-infected mice with the carbonic anhydrase inhibitor acetazolamide reduced lung inflammatory pathology without affecting pendrin synthesis or bacterial loads. Together these data suggest that PT contributes to pertussis pathology through the upregulation of pendrin, which promotes conditions favoring inflammatory pathology. Therefore, pendrin may represent a novel therapeutic target for treatment of pertussis disease.


Subject(s)
Anion Transport Proteins/metabolism , Bordetella pertussis/growth & development , Host-Pathogen Interactions , Pertussis Toxin/metabolism , Whooping Cough/pathology , Whooping Cough/physiopathology , Animals , Anion Transport Proteins/genetics , Bacterial Load , Disease Models, Animal , Gene Expression Profiling , Gene Knockout Techniques , Humans , Infant , Interleukin-17/metabolism , Lung/microbiology , Lung/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/physiopathology , Sulfate Transporters
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