Pertussis Research Articles

Analysis of epidemic characteristics and clinical features of inpatients with pertussis in 2012-2014

Objective To provide basis for the diagnosis, treatment, prevention and control of pertussis by analyzing serological test findings and clinical features of inpatients. Methods Serological test findings (including outpatients and inpatients) of suspected cases and medical records diagnosed as pertussis(severe group and non-severe group) were analyzed in Shandong Provincial Hospital Affiliated to Shandong University from January 1, 2012 to December 31, 2014.This retrospective study was conducted to explore the epidemiological characteristics, clinical manifestations, image manifestations of pertussis in recent years. Results The incidence of pertussis was obviously higher in 2014 than the previous 2 years, nearly 10 times than that of 2013; summer and autumn were high-occurrence seasons; pertussis was found predominately in children under 6 years old, as 68%-80%, and the majority of them were 3 months-1 year old and 4-6 years old, and there was a notable increase in children more than 6 years old in 2014; the clinical manifestations tended to be atypical, primarily spasmodic cough(79.01%, 64/81 cases), cyanosis(60.49%, 49/81 cases), vomiting after cough(35.80%, 30/81 cases), conjunctiva haemorrhage(22.22%, 18/81 cases) apnea or heart rate decrease(9.88%, 8/81 cases), and whooping cough(7.41%, 6/81 cases). There were significant diffe-rences(all P 0.05). Mixed infection with mycoplasma was most common.Imaging manifestations of pertussis were not specific, and they might manifest uneven density, patchy inflammatory infiltrates and atelectasis. Conclusions The morbidity of pertussis is rising and atypical cases is increasing in these years, and severe cases are seen most frequently in small infants, it is necessary to perfect the laboratory test methods and immunization strategy. Key words: Pertussis; Retrospective study; Child

Infant Protection from Maternal Tdap: Timing Matters

Mortality from pertussis is highest in young infants, and previous studies demonstrate that even one dose of pertussis vaccine can protect infants from

Biofilm forming potential and antimicrobial susceptibility of newly emerged Western Australian Bordetella pertussis clinical isolates

Whooping cough caused by Bordetella pertussis is increasing in several countries despite high vaccine coverage. One potential reason for the resurgence is the emergence of genetic variants of the bacterium. Biofilm formation has recently been associated with the pathogenesis of B. pertussis. Biofilm formation of 21 Western Australian B. pertussis clinical isolates was investigated. All isolates formed thicker biofilms than the reference vaccine strain Tohama I while retaining susceptibility to ampicillin, erythromycin, azithromycin and streptomycin. When two biofilm-forming clinical isolates were compared with Tohama I, minimum bactericidal concentrations of antimicrobial agents increased. Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis revealed significant differences in protein expression in B. pertussis biofilms, providing an opportunity for identification of novel biofilm-associated antigens for incorporation in current pertussis vaccines to improve their protective efficacy. The study also highlights the importance of determining antibiograms for biofilms to formulate improved antimicrobial therapeutic regimens.

Increase in pertussis cases along with high prevalence of two emerging genotypes of Bordetella pertussis in Perú, 2012.

BackgroundAs has occurred in many regions worldwide, in 2012 the incidence of pertussis increased in Perú. This epidemiologic situation has been associated with a waning vaccine-induced immunity and the adaptation of Bordetella pertussis to vaccine-induced immunity along with improved diagnostic methods.MethodsThe study comprised a total of 840 pertussis-suspected cases reported in Perú during 2012. We summarize here the distribution of pertussis cases according to age and immunization status along with the immunization-coverage rate. Laboratory diagnosis was performed by culture test and real-time polymerase-chain reaction (PCR). B. pertussis bacteria recovered from infected patients were characterized by pulsed-field gel electrophoresis (PFGE), and the DNA sequencing of the pertussis-toxin (promoter and subunit A), pertactin, and fimbriae (fim2 and fim3) genes.ResultsFrom the total pertussis-suspected cases, 191 (22.7 %) infections were confirmed by real-time PCR and 18 through cultivation of B. pertussis (2.1 %), while one infection of B. parapertussis (0.11 %) was also detected by culture. Pertussis was significantly higher in patients that had had 0–3 vaccine doses (pentavalent vaccine alone) than in those who had had 4–5 vaccine doses (pentavalent plus DwPT boosters) at 94.3 vs. 5.7 %, respectively (p < 0.00001). The relative risk (RR) for patients with 4–5 doses compared to those with fewer than 4 doses or no dose was 0.23 (95 % Confidence Interval: 0.11–0.44), while the vaccine effectiveness was 77 % and coverage 50.5 %. Genetic analysis of B. pertussis isolates from different Peruvian regions detected two clonal groups as identified by PFGE. Those two groups corresponded to the B. pertussis genotypes emerging worldwide ptxP3-ptxA1-prn2 or 9-fim3-1 and ptxP3-ptxA1-prn2 or 9-fim3-2.ConclusionsTwo emerging B. pertussis genotypes similar to isolates involved in worldwide epidemics were detected in Perú. Low vaccine coverage (<50 %) and genetic divergence between the vaccine-producing strain and the local isolates could contribute to this pertussal epidemic.

Study on Toxicity Reduction and Potency Induction in Whole-cell Pertussis Vaccine by Developing a New Optimal Inactivation Condition Processed on Bordetella pertussis.

BackgroundWhooping cough is caused by Bordetella pertussis, and it remains a public health concern. Whole-cell pertussis vaccines have been commonly employed for expanded immunization. There is no doubt of the efficacy of whole cell pertussis vaccine, but it is necessary to improve the vaccine to decrease its toxicity.ObjectivesIn this study, an inactivation process of dealing with pertussis bacteria is optimized in order to decrease the bacteria content in human doses of vaccines and reduce the vaccine’s toxicity.Materials and MethodsThe bacterial suspensions of pertussis strains 509 and 134 were divided into 21 sample parts from F1 to F21 and inactivated under different conditions. The inactivated suspensions of both strains were tested for opacity, non-viability, agglutination, purity, and sterility; the same formulation samples that passed quality tests were then pooled together. The pool of inactivated suspensions were analyzed for sterility, agglutination, opacity, specific toxicity, and potency.ResultsThe harvest of both bacterial strains showed purity. The opacity of various samples were lost under different treatment conditions by heat from 8% to 12%, formaldehyde 6% to 8%, glutaraldehyde 6% to 8%, and thimerosal 5% to 8%. Tests on suspensions after inactivation and on pooled suspensions showed inactivation conditions not degraded agglutinins of both strains. The samples of F2, F4, F8, F12, F15, and F17 passed the toxicity test. The potency (ED50) of these samples showed following order F17 > F12 > F8 > F15, F4 > F2, and F17 revealed higher potency compared to other formulations.ConclusionsIt can be concluded that F17 showed desirable outcomes in the toxicity test and good immunogenicity with a low bacterial number content. Consequently, lower adverse effects and good immunogenicity are foreseeable for vaccine preparation with this method.

Recurrent Cough Syncope Due to Pertussis in Adults: Report of Three Cases and Review of the Literature

Cough syncope, also called “tussive syncope”, is a well-recognized syndrome for about 70 years, in which loss of consciousness usually occurs immediately after a violent cough or prolonged bouts of violent coughing, lasting for seconds with rapid restoration of full consciousness. Its precise pathophysiologic mechanism is not fully understood and remains a matter of debate. Although pertussis is a frequent cause of prolonged cough in adults, still its burden in this age group is under-appreciated and under-diagnosed worldwide. This is well reflected by the fact that despite cough syncope is definitely not rare, until yet only six cases of cough syncope related to pertussis have been reported in the medical literature, one of them by us. We describe additional three adults with recurrent cough syncope due to pertussis who were diagnosed during a period of 3 months which completely resolved by treatment with azithromycin. Diagnosing four cases of cough syncope in adults due to pertussis during a short period in one Department of Internal Medicine, while only five cases were reported from the rest of the world, reflects the great lack of awareness on adult pertussis worldwide. Our four cases indicate that physicians should be much more aware of pertussis as a cause of cough and cough syncope in adults in order to terminate the attacks of cough and cough syncope and its serious complications by adequate antibiotic treatment, as happened with our four patients. J Med Cases. 2016;7(7):266-269 doi: https://doi.org/10.14740/jmc2537w

Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics.

During 2010 and 2012, California and Vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. To overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. Through the use of combined next-generation sequencing technologies, this study compared de novo, single-contig genome assemblies from 31 out of 33 Bordetella pertussis isolates collected during two separate pertussis statewide epidemics and 2 resequenced vaccine strains. Final genome architecture assemblies were verified with whole-genome optical mapping. Sixteen distinct genome rearrangement profiles were observed in epidemic isolate genomes, all of which were distinct from the genome structures of the two resequenced vaccine strains. These rearrangements appear to be mediated by repetitive sequence elements, such as high-copy-number mobile genetic elements and rRNA operons. Additionally, novel and previously identified single nucleotide polymorphisms were detected in 10 virulence-related genes in the epidemic isolates. Whole-genome variation analysis identified state-specific variants, and coding regions bearing nonsynonymous mutations were classified into functional annotated orthologous groups. Comprehensive studies on whole genomes are needed to understand the resurgence of pertussis and develop novel tools to better characterize the molecular epidemiology of evolving B.pertussis populations. IMPORTANCE Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen, B.pertussis strains circulating during epidemics exhibit diversity visible on a genome structural level, previously undetectable by traditional sequence analysis using short-read technologies. For the first time, we combine short- and long-read sequencing platforms with restriction optical mapping for single-contig, de novo assembly of 31 isolates to investigate two geographically and temporally independent U.S. pertussis epidemics. These complete genomes reshape our understanding of B.pertussis evolution and strengthen molecular epidemiology toward one day understanding the resurgence of pertussis.

Plasmacytoid dendritic cell-derived IFNα modulates Th17 differentiation during early Bordetella pertussis infection in mice.

Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). T helper 17 (Th17) cells have a central role in the resolution of the infection. Emerging studies document that type I interferons (IFNs) suppress Th17 differentiation and interleukin (IL)-17 responses in models of infection and chronic inflammation. As plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs, we hypothesize that during B. pertussis infection in mice, pDC-derived IFNα inhibits a rapid increase in Th17 cells. We found that IFNα-secreting pDCs appear in the lungs during the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection or later. The presence of IFNα led to reduced Th17 differentiation and proliferation in vitro. Furthermore, in vivo blocking of IFNα produced by pDCs during infection with B. pertussis infection resulted in early increase of Th17 frequency, inflammation, and reduced bacterial loads in the airways of infected mice. Taken together, the experiments reported here describe an inhibitory role for pDCs and pDC-derived IFNα in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough.

Economic evaluation of outbreak responses of pertussis, tuberculosis and fungal meningitis in New River Valley, Virginia

Economic evaluation of outbreak responses of pertussis, tuberculosis and fungal meningitis in New River Valley, Virginia

Trends in pertussis mortality and morbidity in Colombia, 2002-2012

Whooping cough is a public health problem that mainly affects children under one year of age with highly lethal outcomes. It is a re-emerging disease, which is preventable by immunization.Objective: To analyze mortality and morbidity trends of whooping cough in Colombia between 2002 and 2012.Materials and methods: We conducted a quantitative descriptive study of deaths by pertussis between 2002 and 2012 using data from death certificates registered by the Departamento Administrativo Nacional de Estadística, and cases reported to the Sistema Nacional de Vigilancia en Salud Pública, 2005-2012. Frequency measurements, morbidity and mortality ratios and female increased mortality were calculated.Results: Fifty one point two percent of the deaths occurred in women; the year with more deaths was 2012; 67.3% occurred in urban areas, and 43.5% of the subjects were affiliated to the subsidized health regime. The risk of illness was 1.88 per 1,000 live births with increased risk in Vaupés and Vichada. The risk of death was 0.02 per 1,000 live births; there was a decrease in the lethality trend.Conclusions: Pertussis has reemerged with increasing mortality and morbidity. Since this is a preventable disease through vaccination, it is advisable to increase control and enhance vaccination coverage in both children and adults, who are an important reservoir of the disease. The effective control of pertussisdemands continued work aimed at early identification. It is also necessary to carry out actions to improve data quality in order to facilitate its analysis and the generation of more valid information.

Cost-effectiveness analysis of pertussis outbreak response in New River Health District

Cost-effectiveness analysis of pertussis outbreak response in New River Health District

Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody levels

ABSTRACTThe goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy. Infants received tetanus and pertussis vaccines at 6, 10 and 14 wk of age. TT and PT anti-IgG secretion by infant lymphocytes was measured at 15 wk. Plasma antibodies were measured at 6 wk (pre-vaccination), 15 wk and 1 y of age. Prior to vaccination, TT and PT antibody were detected in 94.6% and 15.2% of infants. At 15 wk anti-TT-IgG and anti-PT-IgG in plasma was increased by 7–9 fold over pre-vaccination levels, while at 1 y plasma anti-TT-IgG was decreased by approximately 5-fold from the peak and had returned to near the pre-vaccination level. At 1 y plasma anti-PT-IgG was decreased by 2-fold 1 yfrom the 15 wk level. However, 89.5% and 82.3% of infants at 1 y had protective levels of anti-TT and anti-PT IgG, respectively. Pre-vaccination plasma IgG levels were associated with lower vaccine-specific IgG secretion by infant lymphocytes at 15 wk (p < 0.10). This apparent inhibition was seen for anti-TT-IgG at both 15 wk (p < 0.05) and t 1 y (p < 0.10) of age. In summary, we report an apparent inhibitory effect of passively derived maternal antibody on an infants' own antibody response to the same vaccine. However, since the cut-off values for protective titers are low, infants had protective antibody levels throughout infancy.

Insertional inactivation of virulence operon in population of persistent Bordetella pertussis bacteria

Avirulent B. pertussis bacteria containing IS elements in the bvgAS operon were detected during the study of whooping cough patients and bacilli carriers. The present work is devoted to the study of the accumulation dynamics and the mechanisms of generation of persistent forms of the B. pertussis bacteria in lower monkeys as the most adequate model for extrapolation ofthe experiment results to humans. By means of the real-time PCR method, it was established that the B. pertussis bacteria lived more than three months in the upper respiratory tract after a single intranasal monkey infection; the period was reduced to 14-28 days during repeated infection. An increase in the portion of B. pertussis Bvg mutants in the population to tens of percent from the total number of registered bacteria was registered. The experimental confirmation ofthe development and accumulation of avirulent B. pertussis Bvg mutants during the development of the infectious process was obtained. Further study of the composition of the B. pertussis persistent bacteria population at different stages of the disease will make it possible to formulate new approaches to the whooping cough diagnostics and prevention and creation of fundamentally new drugs.

The "100 Days Cough" Was Not Originally Whooping Cough.

The "100 Days Cough" Was Not Originally Whooping Cough.

Whooping cough, twenty years from acellular vaccines introduction.

Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years.

Association of Vitamin D Receptor Polymorphism with Susceptibility to Symptomatic Pertussis.

Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1–10% in the general population, notifications of symptomatic pertussis only comprise 0.01–0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFα, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D3 (VD3) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection.

The role of B. pertussis vaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development

ABSTRACTWhooping cough, or pertussis, caused by Bordetella pertussis is considered resurgent in a number of countries world-wide, despite continued high level vaccine coverage. Among a number of causes for this that have been proposed, is the emergence of B. pertussis strains expressing variants of the antigens contained in acellular pertussis vaccines; i.e. the evolution of B. pertussis toward vaccine escape. This commentary highlights the contradictory nature of evidence for this but also discusses the importance of understanding the role of B. pertussis adaptation to vaccine-mediated immune selection pressures for vaccine-mediated pertussis control strategies.

Is Pertussis Associated With Later Epilepsy?

Is Pertussis Associated With Later Epilepsy?

Structural Investigation into Calmodulin's Role in Activating Bordetella Pertussis Adenylyl Cyclase Toxin CyaA

Whooping cough is a respiratory disease resulting from Bordetella pertussis infection that remains a globally significant cause of vaccine-preventable deaths. As a major virulence factor, the adenylyl cyclase toxin (ACT) of Bordetella pertussis (CyaA) has evolved a unique mode of activation by host cell calmodulin (CaM), thereby making it a potential target for the design of novel therapeutics. Currently, no high-resolution structure of intact CaM bound to CyaA exists, so the molecular pathways controlling enzymatic activation remain unclear. Previously, we have identified unique sites of intermolecular association between CyaA and CaM that directly impact CaM's structure, metal-binding properties, and conformational stability. In this study, we utilized site-directed mutagenesis, biophysical, and biochemical techniques to investigate the roles of metal-binding and CaM-dependent interactions in regulating CyaA structure and function. Site-specific mutations mapping to metal-binding site I or II of CaM reduced CyaA binding affinity and cAMP production without significantly altering CaM conformation. Moreover, inactivation of sites I or II in CaM modulated the global conformation of the CaM/CyaA complex in a metal-dependent manner. In the absence of CaM, CyaA exhibited multiple thermal transitions during unfolding experiments, but domain-specific interactions with wild-type or mutant CaM increased the thermal stability of the complex. Together, these data support that CaM-dependent CyaA activation occurs by novel structural mechanisms. This study sheds light on the molecular details of CaM-regulated ACTs, knowledge which may be exploited in the rationale design of inhibitory compounds.

Pertussis vaccination coverage among Australian women prior to childbirth in the cocooning era: a two-hospital, cross-sectional survey, 2010 to 2013.

Recent pertussis epidemics have triggered implementation of cocooning, involving caregiver vaccination to indirectly protecting susceptible infants. To determine patient, provider and setting factors associated with maternal pertussis booster vaccination (dTpa) within 5-10 years before childbirth. Cross-sectional survey using Health Belief Model constructs among postpartum women in a tertiary referral centre and a private hospital in Sydney, Australia. Pertussis vaccination was current among 33.7% of the 2483 new mothers (0.5% vaccinated during pregnancy). Women were more likely to be vaccinated if they had heard of 'whooping cough' from a health professional (OR: 2.59, P < 0.001, 95% CI: 1.70-3.95), were recommended the vaccine (OR: 2.48, P < 0.00, 95% CI: 1.55-4.00), perceived pertussis as 'severe' for adults (OR: 1.21, p0.009, 95% CI: 1.05-1.39) and 'common' within their community (OR: 1.38, P < 0.001, 95% CI: 1.18-1.61). They more often agreed that it was their parental responsibility to be vaccinated (OR: 1.61, P = 0.002, 95% CI: 1.19-2.18), and this would help prevent their baby from contracting pertussis (OR: 1.22, P = 0.046, 95% CI: 1.00-1.47). Vaccinated women were less likely to report vaccination barriers: time constraints (OR: 0.75, P < 0.001, 95% CI: 0.66-0.85) and having safety concerns (OR: 0.80, P < 0.001, 95% CI: 0.69-0.92). Additionally, their partners reported three times higher uptake (76% vs 49%; P < 0.001; 95% CI: 2.66-3.85). Current pertussis vaccination in only one in every three postpartum participants may indicate insufficient coverage to protect newborns. Practitioners are instrumental in raising awareness and addressing vaccine concerns. Integrating vaccination into routine obstetric care, whether antenatally or postnatally, may minimise barriers.