Pertussis Infection Research Articles

Looking beyond Pertussis in Prolonged Cough Illness of Young Children.

Pertussis, commonly known as whooping cough, is one of the most poorly controlled vaccine-preventable diseases in the world. South-East Asia is estimated to contribute the most to childhood disease burden while this remains largely unexplored in India. The clinical diagnosis of pertussis in young children is a challenge as the classical four-stage presentation with paroxysmal cough or whoop may be absent. It is also difficult to differentiate from other respiratory infections which can cause pertussis-like illness. Children below two years with prolonged cough illness attending an urban pediatric center in western India, were evaluated for pertussis and viral infections by molecular methods. Bordetella pertussis and B. holmesii were confirmed in three each of 45 suspected cases, and RSV-A and hMPV were the most common viruses that were detected. These organisms can mimic mild cases of pertussis and need to be considered in differential diagnosis of prolonged cough illness in young children. The accurate etiology of prolonged cough illness needs to be detected and documented to ensure appropriate management and accurate estimates of disease burden.

A putative link between pertussis and new onset of gastroesophageal reflux an observational study.

BackgroundPertussis is an infectious disease of the respiratory tract with a changing epidemiology. An increasing incidence has been found in the adult population with recurrent infections possibly related to changes in the current vaccine. Is there an association between pertussis infection, refractory cough and atypical gastro-oesophageal reflux (GORD)? Does this magnify and compound respiratory complications?MethodsObservational study which compares post-pertussis (n=103) with non-pertussis patients (n=105) with established GORD. Patients were assessed for laryngopharyngeal reflux and aspiration of refluxate by a novel scintigraphic study.ResultsBoth groups showed severe GORD in association with high rates of laryngopharyngeal reflux (LPR) and pulmonary aspiration and lung disease. High rates of hiatus hernia and clinical diagnosis of “atypical” asthma showed correlations with pulmonary aspiration.ConclusionsA high level of new onset LPR and lung aspiration has been shown in patients with chronic cough after recent pertussis infection by a novel scintigraphic technique with fused hybrid x-ray computed tomography (SPECT/CT).

Laboratory Performance and Clinical Correlation of Real-time Polymerase Chain Reaction as a Diagnostic Test for Bordetella Pertussis Isolated from Patients in Oman.

ObjectivesTo evaluate real-time polymerase chain reaction (PCR) as a diagnostic tool for pertussis (whooping cough), vis-à-vis culture, the long-time gold standard, with emphasis on the importance of clinical correlation in determining specificity.MethodsNasopharyngeal/throat swab samples in charcoal media received from all over Oman at Central Public Health Laboratories from January 2014 to December 2016 were included in this study. These samples were tested using both culture and real-time PCR. PCR was compared with culture to calculate its sensitivity and specificity. Further clinical correlation was conducted for the discrepant cases using different case definitions.ResultsA total of 590 nasopharyngeal/throat samples were included in the study. Out of the 590 samples, 73 were positive by PCR compared with 26 positive samples by culture (which were also positive by PCR). The sensitivity and specificity of PCR compared with those of culture were 100% (95% CI: 86.77−100) and 91.7% (95% CI: 89.07−93.81), respectively. To rule out false-positive results by PCR, clinical correlation was performed. Out of 47 cases that were positive by PCR but negative by culture, 44 cases were clinically evaluated by accessing clinical details. Out of these 44 cases, 21 (47.7%) met the pertussis clinical criteria according to the CDC-2014 case definition, 41 (93.2%) according to the Europe-2008 case definition, and 44 (100%) according to the Canada-2009 and Australia-2014 case definitions. With only positive PCR, these cases were classified as confirmed according to these case definitions, which increased the specificity of PCR to 95.7–100%. The mean turnaround time was 3.5 days for PCR compared to 6.2 days for culture.ConclusionsReal-time PCR is a highly sensitive and specific test for the diagnosis of Bordetella pertussis infection. Based on our results, we recommend setting up PCR diagnostic facilities in regional hospitals in Oman as this will lead to a timely and accurate diagnosis of pertussis.

Seroprevalence of Pertussis in Adults at Childbearing Age Pre- and Post- COVID-19 in Beijing, China.

The number of reported pertussis cases has significantly decreased during the coronavirus disease 2019 (COVID-19) pandemic under the influence of strict public health measures in many countries including China. This study evaluated the prevalence of serum anti-pertussis toxin (anti-PT) IgG antibodies in adults at childbearing age pre- and post- COVID-19 in Beijing, China. Altogether, 2021 serum samples collected from individuals aged 20 to 39 years who attended an annual health examination at the Sixth Medical Center of PLA General Hospital, Beijing, in 2018~2020 were measured by ELISA. The median concentration of anti-PT IgG antibodies among participants in 2020 (2.96 IU/mL) was significantly lower than that in 2018 (3.27 IU/mL) (p = 0.011) and in 2019 (3.24 IU/mL) (p = 0.014). The percentage of participants with anti-PT IgG antibodies higher than 40 IU/mL (indicating a pertussis infection within the past few years) was 1.79% (9/503) in 2018, 2.04% (15/735) in 2019 and 1.66% (13/783) in 2020, respectively. The corresponding numbers of the non-detectable (<5 IU/mL) rate of anti-PT IgG antibodies were 66.60%, 65.99% and 70.24%. Our results showed that there was a significant difference between true and reported incidence rates even during the COVID-19 pandemic. The proportion of adults at childbearing age without pertussis-specific antibodies is high, suggesting that booster vaccinations in adults should be considered in this country.

Long Lasting Antibodies From Convalescent Pertussis Patients Induce ROS Production and Bacterial Killing by Human Neutrophils.

Pertussis is a respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Despite high vaccination coverage this disease remains a public health concern worldwide. A better understanding of the protective immune responses to B. pertussis is required for the development of improved vaccines. The aim of this study was to determine the production of reactive oxygen species (ROS) by human neutrophils in response to B. pertussis and to determine the contribution of opsonizing antibodies from convalescent pertussis patients in this response. The serum samples from convalescent patients were taken at <3, 9, 18 and 36 months after diagnosis of pertussis. Also included were sera from healthy age-matched controls. We show that neutrophils produced high levels of ROS in response to opsonized, compared to non-opsonized, B. pertussis and that this effect was independent of the time the convalescent serum samples were taken. This indicates the presence of functional opsonizing antibodies up to 3 years after B. pertussis infection. While opsonization of B. pertussis with serum samples from uninfected controls also induced ROS production, sera from infected individuals induced significantly higher ROS levels. Spearman correlations analysis showed that IgG antibodies targeting fimbriae3 followed by pertactin, and BrkA correlate with ROS production. Additionally, we observed that neutrophils killed opsonized B. pertussis in a ROS-dependent manner. Searching for other antigen-specific antibodies from convalescent pertussis patients involved in ROS production by neutrophils may assist in the identification of novel antigens to improve the current pertussis vaccines.

Safety and immunogenicity of live intranasal pertussis vaccine GamLVP in the experimental infant hamadryas baboon model

Introduction. The Gamaleya National Center of Epidemiology and Microbiology has developed a live intranasal pertussis vaccine, GamLVP, for protection against whooping cough. It is indicated for vaccination of infants and revaccination of adults of all age groups. Preclinical studies on suckling mice or rats and adult monkeys as well as clinical trials involving adult volunteers demonstrated safety and efficacy of the GamLVP vaccine. The expansion of the GamLVP vaccine to be used for vaccination of infants requires additional preclinical studies to assess its safety and immunogenicity in the most suitable experimental model of infant hamadryas baboons (Papio hamadryas).The aim of the study was to assess safety and immunogenicity of the GamLVP vaccine administered intranasally for a single dose, two-dose, and three-dose immunization of P. hamadryas infants.Materials and methods. The study was performed in three 1–2-month-old P. hamadryas infants kept, together with their mothers, in a separate cage. The results of the complete blood count and biochemical profile tests were measured before and after the immunization and experimental infection. The enzyme immunoassay (EIA) was used to detect any changes in the levels of specific IgG antibodies in sera from the mothers and infants; the agglutination test (AT) was used to measure titers of total anti-pertussis antibodies.Results. The intranasal immunization of P. hamadryas infants with the GamLVP vaccine triggered development of a specific humoral immune response mediated by IgG antibodies (pertussis toxin + filamentous hemagglutinin), increased titers of total agglutinating anti-pertussis antibodies, caused no local and systemic reactions, caused no changes in the complete blood count and biochemical profile. The experimental infection of the GamLVPimmunized P. hamadryas infants did not cause any changes in the laboratory blood test values and any clinical manifestations typical of the pertussis infection.

Decay of anti-Bordetella pertussis antibodies in women of childbearing age following COVID-19 non-pharmaceutical measures

BackgroundImmunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans-placental transfer of anti-B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic. MethodsPaired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti-B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1st trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti-B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p < 0.016 using Bonferroni correction. ResultsAnnual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (<1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95 %CI, 4.2–10.9) vs. 8.4 IU/ml (5.1–13.9; p = 0.004); 18.8 IU/ml (10.9–32.2) vs. 23.6 IU/ml (13.2–42.1; p < 0.001); and 37.1 IU/ml (18.1–75.9) vs. 47.2 IU/ml (24.8–89.9; p = 0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018–2019, 8.4 IU/ml (95% CI, 5.1–13.9) vs. 5.4 IU/ml (95% CI, 3.8–7.7; p = 0.166), 23.6 IU/ml (95% CI, 13.2–42.1) vs. 20.1 IU/ml (95% CI, 13.4–30.2; p = 0.656), and 47.2 IU/ml (24.8–89.9) vs. 17.3 IU/ml (95% CI, 10.5–28.7; p = 0.021), respectively. DiscussionB. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19.

Long-Term Immunogenicity upon Pertussis Booster Vaccination in Young Adults and Children in Relation to Priming Vaccinations in Infancy.

Booster vaccinations for pertussis are advised in many countries during childhood or adulthood. In a phase IV longitudinal interventional study, we assessed long-term immunity following an extra pertussis booster vaccination in children and adults. Children (9 years of age) were primed in infancy with either the Dutch whole cell pertussis (wP) vaccine (n = 49) or acellular pertussis (aP) vaccines (n = 59), and all children received a preschool aP booster. Adults (25–29 years, n = 86) were wP-primed in infancy and did not receive a preschool booster. All were followed-up for approximately 6 years. After the additional booster, antibody responses to pertussis were more heterogeneous but generally higher in adults compared with children, and additional modelling showed that antibody concentrations remained higher for at least a decade. Serologic parameters indicative of recent pertussis infection were more often found in aP-primed children (12%) compared with wP-primed individuals (2%) (p = 0.052). This suggests that the aP booster vaccination in aP-primed children offers less long-term protection against pertussis infection and consequently against transmission. Together, these data show that aP priming in combination with aP boosting may not be sufficient to prevent circulation and transmission, while wP-primed adults may benefit from enhanced long-lasting immunity.

Maternal Gestational Tdap Vaccination and Autism: A Critique of Becerra-Culqui et al. (2018)

We report flaws and inconsistencies in a critically important study of autism risk following maternal Tdap vaccination. The authors of the 2018 study, Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination and Autism Spectrum Disorder (BC18), concluded that Tdap gestational vaccination is not associated with increased autism risk and claimed to provide “evidence supporting the ACIP’s recommendation to vaccinate pregnant women”. Our observations, based on information from the study itself, challenge these conclusions. We find evidence of a peculiar study design and approach to data analysis forcing outcomes by arbitrary data adjustments, overlooked variables of importance such as Bordetella pertussis infection prevalence and vaccine injury rates, insufficient consideration of likely interactions between multiple historical medical challenges by vaccines and other interventions on their participants, exclusion from the study individuals likely at risk of vaccine intolerance due to genetics, and indications that the study samples were not representative of the general population. Their first-year data show a concerning spike in ASD rates, and their findings and conclusions did not hold up to real-world data, which currently reports 3.8% ASD rate in California. Our observations, based on information from the study itself, challenge the conclusions of Becerra-Culqui et al, 2018.

A Retrospective Cohort Study on Infant Respiratory Tract Infection Hospitalizations and Recurrent Wheeze and Asthma Risk: Impact of Respiratory Syncytial Virus.

Infant respiratory syncytial virus infection (RSV) has been associated with asthma later in life. We explored the risk of recurrent wheeze or asthma in children with infant RSV-associated hospitalization compared to other respiratory infections. We performed a retrospective cohort study using Danish national hospital discharge registers. Infants younger than 6 months, born between January 1995 and October 2018, and with a RSV hospital admission were compared to infants hospitalized for injuries, non-RSV acute upper respiratory tract infection (AURTI), pneumonia and other respiratory pathogens, nonpathogen-coded lower respiratory tract infections (LRTI), pertussis, or nonspecific respiratory infections. Infants were followed until recurrent wheeze or asthma diagnosis, death, migration, age 10 years, or study end. We estimated cumulative incidence rate ratios (CIRR) and hazard ratios (HR) adjusted for sex, age at inclusion, hospital length of stay (LOS), maternal smoking, 5-minute APGAR score (APGAR5), prematurity, and congenital risk factors (CRF). We included 68 130 infants, of whom 20 920 (30.7%) had RSV hospitalization. The cumulative incidence rate of recurrent wheeze or asthma was 16.6 per 1000 person-years after RSV hospitalization, higher than after injury (CIRR, 2.69; 95% confidence interval [CI], 2.48-2.92), AURTI (CIRR, 1.48; 95% CI, 1.34-1.58), or pertussis (CIRR, 2.32; 95% CI, 1.85-2.91), similar to pneumonia and other respiratory pathogens (CIRR, 1.15; 95% CI, .99-1.34) and LRTI (CIRR, 0.79; 95% CI, .60-1.04), but lower than nonspecific respiratory infections (CIRR, 0.79; 95% CI, .73-.87). Adjusted HRs for recurrent wheeze or asthma after RSV hospitalization compared to injuries decreased from 2.37 (95% CI, 2.08-2.70) for 0 to <1 year to 1.23 (95% CI, .88-1.73) for 6 to <10 years for term-born children, and from 1.48 (95% CI, 1.09-2.00) to 0.60 (95% CI, .25-1.43) for preterm-born children. Sex, maternal smoking, LOS, CRF, and APGAR5 were independent risk factors. Infant RSV hospitalization is associated with recurrent wheeze and asthma hospitalization, predominantly at preschool age. If causal, RSV prophylaxis, including vaccines, may significantly reduce disease burden of wheeze and asthma.

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model.

Pertussis, caused by the gram-negative bacterium Bordetella pertussis, is a highly contagious respiratory disease. Intranasal vaccination is an ideal strategy to prevent pertussis, as the nasal mucosa represents the first-line barrier to B. pertussis infection. The current intramuscular acellular pertussis (aP) vaccines elicit strong antibody and Th2-biased responses but not necessary cellular and mucosal immunity. Here, we formulated two cyclic dinucleotide (CDN)-adjuvanted aP subunit vaccines, a mammalian 2’,3’-cGAMP-adjuvanted aP vaccine and a bacterial-derived c-di-GMP-adjuvanted aP vaccine, and evaluated their immunogenicity in a mouse model. We found that the aP vaccine alone delivered intranasally (IN) induced moderate systemic and mucosal humoral immunity but weak cellular immunity, whereas the alum-adjuvanted aP vaccine administered intraperitoneally elicited higher Th2 and systemic humoral immune responses but weaker Th1 and Th17 and mucosal immune responses. In contrast, both CDN-adjuvanted aP vaccines administered via the IN route induced robust humoral and cellular immunity systemically and mucosally. Furthermore, the c-di-GMP-adjuvanted aP vaccine generated better antibody production and stronger Th1 and Th17 responses than the 2′,3′-cGAMP-adjuvanted aP vaccine. In addition, following B. pertussis challenge, the group of mice that received IN immunization with the c-di-GMP-adjuvanted aP vaccine showed better protection than all other groups of vaccinated mice, with decreased inflammatory cell infiltration in the lung and reduced bacterial burden in both the upper and lower respiratory tracts. In summary, the c-di-GMP-adjuvanted aP vaccine can elicit a multifaceted potent immune response resulting in robust bacterial clearance in the respiratory tract, which indicates that c-di-GMP can serve as a potential mucosal adjuvant for the pertussis vaccine.

Multidimensional Frailty and Vaccinations in Older People: A Cross-Sectional Study.

It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association are still missing. Therefore, we aimed to investigate the prevalence of four recommended vaccinations (influenza, herpes zoster, pneumococcal and diphtheria-tetanus-pertussis) and the association with multidimensional frailty assessed using a self-reported comprehensive geriatric assessment tool, i.e., the multidimensional prognostic index (SELFY-MPI). Older participants visiting the outpatient clinic of Azienda Ospedaliera Universitaria, Palermo, Italy were included. The SELFY-MPI questionnaire score was calculated based on eight different domains, while the vaccination status was determined using self-reported information. We included 319 participants from the 500 initially considered (63.8%). Vaccination against influenza was observed in 70.5% of the cases, whilst only 1.3% received the vaccination against diphtheria-tetanus-pertussis. Participants with higher SELFY-MPI scores were more likely to report vaccination against pneumococcus (45.6 vs. 28.3%, p = 0.01), whilst no significant differences were observed for the other vaccinations. In conclusion, the coverage of recommended vaccinations is low. Higher SELFY-MPI scores and vaccination status, particularly anti-pneumococcus, appear to be associated, but future studies are urgently needed for confirming that frailty is associated with vaccination status in older people.

Bordetella pertussis-infected innate immune cells drive the anti-pertussis response of human airway epithelium

Pertussis is a severe respiratory tract infection caused by Bordetella pertussis. This bacterium infects the ciliated epithelium of the human airways. We investigated the epithelial cell response to B. pertussis infection in primary human airway epithelium (HAE) differentiated at air–liquid interface. Infection of the HAE cells mimicked several hallmarks of B. pertussis infection such as reduced epithelial barrier integrity and abrogation of mucociliary transport. Our data suggests mild immunological activation of HAE by B. pertussis indicated by secretion of IL-6 and CXCL8 and the enrichment of genes involved in bacterial recognition and innate immune processes. We identified IL-1β and IFNγ, present in conditioned media derived from B. pertussis-infected macrophage and NK cells, as essential immunological factors for inducing robust chemokine secretion by HAE in response to B. pertussis. In transwell migration assays, the chemokine-containing supernatants derived from this HAE induced monocyte migration. Our data suggests that the airway epithelium on its own has a limited immunological response to B. pertussis and that for a broad immune response communication with local innate immune cells is necessary. This highlights the importance of intercellular communication in the defense against B. pertussis infection and may assist in the rational design of improved pertussis vaccines.

Burden of whooping cough in China (PertussisChina): study protocol of a prospective, population-based case–control study

IntroductionPertussis is one of the top 10 diseases of children under 10 years of age, and the few vaccine-preventable diseases who is on a rise in China in recent years;...

Impact of the COVID-19 pandemic on Bordetella pertussis infections in England

BackgroundIn March 2020, England went into its first lockdown in response to the COVID-19 pandemic. Restrictions eased temporarily, followed by second and third waves in October 2020 and January 2021. Recent data showed that the COVID-19 pandemic resulted in reduced transmission of some invasive diseases. We assess the impact of the COVID-19 pandemic on pertussis incidence and on the immunisation programme in England.MethodsWe assessed trends in pertussis cases from 2012 to 2020 by age group and month. Incidence from the time that England eased its initial lockdown measures in July 2020 through to summer 2021 was calculated and the incidence rate ratios of pertussis cases from five years prior to the pandemic (July 2014 – June 2019) compared to the same time period during the pandemic (July 2020 – June 2021). Vaccine coverage estimates for pertussis containing vaccines were reviewed for the maternal and childhood programmes.ResultsA substantial decline in pertussis cases was observed from April 2020 onwards, marking the lowest number of cases in the last decade. Pertussis incidence dropped in all age groups, particularly among infants less than one year old (0.50 / 100,000 during July 2020 to June 2021 compared to 24.49/ 100,000 from July 2014 to June 2019). The incidence rate ratio was 0.02 (95% CI 0.01 to 0.02) for July 2014 to June 2019 (pre-pandemic) compared to the pandemic period of July 2020 to June 2021. None of the cases had a co-infection with SARS-CoV-2. Vaccine coverage for infants born between January to March 2020 with three doses of pertussis vaccine by 12 months of age decreased by 1.1% points compared to infants born between January to March 2019 (91.6% and 92.7%, respectively). Prenatal pertussis coverage for the 2020 to 2021 financial year was 2.7% points lower than the year prior to the pandemic (70.5% and 76.8%, respectively).ConclusionsLockdown measures due to the COVID-19 pandemic have had a significant impact on pertussis transmission. With the easing of restrictions it is important to continue monitoring pertussis cases in England alongside coverage of the maternal and childhood immunisation programmes.

Modulation of Inflammatory Signaling Molecules in Bordetella pertussis Antigen-Challenged Human Monocytes in Presence of Adrenergic Agonists.

BscF is a type III secretion system (T3SS) needle protein from Bordetella pertussis and has previously been shown to induce a sufficient Th1 and Th17 response in human monocytes and mice as a prerequisite for long-lasting protective immunity against pertussis infection. In our current study, we aim to compare the modulation of inflammatory signaling molecules as a direct measure of the immune response to the B. pertussis antigens BscF and Tdap in the presence or absence of the adrenergic receptor agonists phenylephrine (PE) or isoproterenol (ISO) to observe differences that may contribute to the diminished protective immunity of the current acellular pertussis (aP) vaccine, Tdap. Stimulation of human monocyte THP-1 cells with LPS, BscF, and Tdap induced a robust elevation of CCL20, CXCL10, PGE2, and PGF2α among most chemokine and prostanoid members when compared with the control treatment. Treatment with the adrenergic agonist PE or ISO significantly enhanced the BscF- and Tdap-stimulated modulation of CCL20 and CXCL10 but not PGE2 and PGF2α, suggesting that adrenergic modulation of pertussis antigen responses might be a new therapeutic strategy to improve the longevity of pertussis immunity. Stimulation of THP-1 cells with BscF alone initiated significant expression of CXCL10 and PGF2α but not when Tdap was used, suggesting that BscF might be an important pertussis antigen for next-generation pertussis vaccines or when combined with the current aP vaccine. Our data offer opportunities for designing new therapeutic approaches against pertussis infection.

Antibodies binding diverse pertactin epitopes protect mice from Bordetella pertussis infection

Infection by the bacterium Bordetella pertussis continues to cause considerable morbidity and mortality worldwide. Many current acellular pertussis vaccines include the antigen pertactin, which has presumptive adhesive and immunomodulatory activities, but is rapidly lost from clinical isolates after the introduction of these vaccines. To better understand the contributions of pertactin antibodies to protection and pertactin's role in pathogenesis, we isolated and characterized recombinant antibodies binding four distinct epitopes on pertactin. We demonstrate that four of these antibodies bind epitopes that are conserved across all three classical Bordetella strains, and competition assays further showed that antibodies binding these epitopes are also elicited by B. pertussis infection of baboons. Surprisingly, we found that representative antibodies binding each epitope protected mice against experimental B. pertussis infection. A cocktail of antibodies from each epitope group protected mice against a subsequent lethal dose of B. pertussis and greatly reduced lung colonization levels after sublethal challenge. Each antibody reduced B. pertussis lung colonization levels up to 100-fold when administered individually, which was significantly reduced when antibody effector functions were impaired, with no antibody mediating antibody-dependent complement-induced lysis. These data suggest that antibodies binding multiple pertactin epitopes protect primarily by the same bactericidal mechanism, which overshadows contributions from blockade of other pertactin functions. These antibodies expand the available tools to further dissect pertactin's role in infection and understand the impact of antipertactin antibodies on bacterial fitness.

Pertussis outbreak investigation in Northwest Ethiopia: A community based study.

BackgroundPertussis or whooping cough is a vaccine-preventable, highly contagious, respiratory illness caused by Bordetella pertussis or Bordetella parapertussis. Infants and young children have remained most susceptible to pertussis-related morbidity and mortality. The aim of this study was to investigate pertussis infection and analyze the associated factors involved in the occurrence of the cases.MethodsCommunity-based case-control was conducted in Dahena district, Northwest Ethiopia, from March 27—April 30, 2019. All cases ages 1–18 years old were identified by using the clinical standard case definition of pertussis adopted from World Health Organization (WHO). Data was collected using a structured questionnaire via face-to-face interviews. The data collected was cleaned, coded and entered into Epi info version 7.2.1.0 and exported to SPSS version 23 for statistical analysis. Bivariable and multivariable logistic regression analysis were employed to identify predictors. Factors with a p-value of < 0.05 were considered as independent risk factors of pertussis infection in multivariable logistic regression analysis.ResultA total of 122 pertussis cases were enrolled from the Azila cluster of the Dahena district. Of these figures, 64 (52.5%) were females. The overall attack rate (AR) of pertussis cases in the cluster was 8.6/10000 population. The sex-specific AR of females was 8.9/10000 population. The multivariable logistic regression analysis showed that; being unvaccinated 4.17 (AOR, 4.17, 95% CI, 1.914–9.091), contact to cases 2.93 (AOR: 2.93, 95% CI 1.223–6.996), and living in a house with no window 2.6 (AOR: 2.6(95% CI 1.071 to 6.322) were the independent significantly risk factors for pertussis infection.ConclusionThe contributing factor for pertussis infection was associated with case-contact, living in the house without windows and being unvaccinated. Wag Hemra Zone and Dahena district health office should encourage the vaccination activities of the cluster health center and awareness for the community should be practiced to limit disease transmission.

Loop-Mediated Isothermal Amplification Coupled With Nanoparticle-Based Lateral Biosensor for Rapid, Sensitive, and Specific Detection of Bordetella pertussis.

Bordetella pertussis is the most frequent causative agent for pertussis, which is a highly contagious disease. Here, we developed a method based on loop-mediated isothermal amplification (LAMP) and nanoparticle-based lateral flow biosensor (LFB) for the timely diagnosis of B. pertussis infections. A set of six primers was designed for LAMP reactions, and the LAMP results were rapidly and visually indicated using LFB. The recommended condition for the B. pertussis LAMP reactions is 40 min at 66°C. Our results confirmed that the LAMP-LFB assay could specifically detect B. pertussis and did not cross-react with non-B. pertussis isolates. The sensitivity of the B. pertussis LAMP-LFB assay was 50 fg per reaction. In particular, 108 nasopharyngeal swab (NPS) samples were collected to evaluate the B. pertussis LAMP-LFB assay, and the results were compared with those of the quantitative PCR (qPCR) method. The positive rates of B. pertussis LAMP-LFB and qPCR were 40.7% and 38.8%, respectively, and the agreement between the LAMP-LFB and qPCR results was 98%, with a kappa value of 0.96. The whole process of LAMP-LFB can be completed within 1 h, which is much shorter than that of qPCR, including about 15 min of rapid DNA extraction, 40 min of LAMP reaction, and within 2 min of the LFB test. Collectively, the B. pertussis LAMP-LFB assay developed in this report offers a new option for the rapid, reliable, and simple diagnosis of B. pertussis infections.

Reduced Bordetella pertussis-specific CD4+ T-Cell Responses at Older Age.

Pertussis, a human-specific respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis (Bp), remains endemic with epidemic years despite high vaccination coverage. Whereas pertussis vaccines and natural infection with Bp confer immune protection, the duration of protection varies and is not lifelong. Recent evidence indicates a considerable underestimation of the pertussis burden among older adults. Whereas the impact of increasing age on Bp-specific humoral immunity has been demonstrated, little is known on immunosenescence of CD4+ T-cell responses in the context of Bp. Here, we aimed to address whether increasing age impacts responsiveness of the Bp-specific CD4+ T-cells in the memory pool following a clinically symptomatic pertussis infection in whole cell vaccine-primed pediatric and adult cases. Cytokine and proliferative responses and phenotypical profiles of CD4+ T cells specific for Bp antigens at an early and late convalescent timepoint were compared. Responses of various Th cytokines, including IFNγ, were significantly lower in older adults at early and late timepoints post diagnosis. In addition, we found lower frequencies of Bp-specific proliferated CD4+ T cells in older adults, in the absence of differences in replication profile. Phenotyping of Bp-specific CD4+ T cells suggested reduced expression of activation markers rather than increased expression of co-inhibitory markers. Altogether, our findings show that the magnitude and functionality of the Bp-specific memory CD4+ T-cell pool decrease at older age. Declined CD4+ T-cell responsiveness to Bp is suggested to contribute to the burden of pertussis in older adults.