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The Journal of Infectious Diseases Sep 2021Pertussis (whooping cough) is a respiratory infection caused by Bordetella pertussis. All ages are susceptible. In the prevaccine era, almost all children became...
Pertussis (whooping cough) is a respiratory infection caused by Bordetella pertussis. All ages are susceptible. In the prevaccine era, almost all children became infected. Pertussis is particularly dangerous in young infants, who account for practically all hospitalizations and deaths, but clinical disease is burdensome at any age. Widespread use of pertussis vaccines dramatically reduced cases, but concern over adverse reactions led to the replacement of standard whole-cell by acellular pertussis vaccines that contain only a few selected pertussis antigens and are far less reactogenic. Routine administration of acellular pertussis vaccines combined with diphtheria and tetanus toxoids is recommended in infancy with toddler and preschool boosters, at age 11, and during pregnancy. Boosting in the second half of every pregancy is critical to protection of the newborn. Waning of vaccine immunity over time has become an increasing concern, and several new pertussis vaccines are being evaluated to address this problem.
Topics: Bordetella pertussis; Child; Child, Preschool; Diphtheria-Tetanus-Pertussis Vaccine; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Immunization, Secondary; Infant; Male; Pertussis Vaccine; Vaccine-Preventable Diseases; Whooping Cough
PubMed: 34590129
DOI: 10.1093/infdis/jiaa469 -
Clinical Infectious Diseases : An... Jun 2020Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the...
BACKGROUND
Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the risk diphtheria poses when civil unrest interrupts vaccination and healthcare access. Lack of interest over the last century resulted in knowledge gaps about diphtheria's epidemiology, transmission, and control.
METHODS
We conducted 9 distinct systematic reviews on PubMed and Scopus (March-May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps.
RESULTS
We identified 6934 articles, reviewed 781 full texts, and included 266. From this, we estimate that the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% credible interval [CrI], 17.7-19.4 days), and 95% clear Corynebacterium diphtheriae within 48 days (95% CrI, 46-51 days). Asymptomatic carriers cause 76% (95% confidence interval, 59%-87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7-4.3. Receipt of 3 doses of diphtheria toxoid vaccine is 87% (95% CrI, 68%-97%) effective against symptomatic disease and reduces transmission by 60% (95% CrI, 51%-68%). Vaccinated individuals can become colonized and transmit; consequently, vaccination alone can only interrupt transmission in 28% of outbreak settings, making isolation and antibiotics essential. While antibiotics reduce the duration of infection, they must be paired with diphtheria antitoxin to limit morbidity.
CONCLUSIONS
Appropriate tools to confront diphtheria exist; however, accurate understanding of the unique characteristics is crucial and lifesaving treatments must be made widely available. This comprehensive update provides clinical and public health guidance for diphtheria-specific preparedness and response.
Topics: Child; Diphtheria; Disease Outbreaks; Humans; Vaccination
PubMed: 31425581
DOI: 10.1093/cid/ciz808 -
The Journal of Experimental Medicine Oct 2023The ZAKα-driven ribotoxic stress response (RSR) is activated by ribosome stalling and/or collisions. Recent work demonstrates that RSR also plays a role in innate...
The ZAKα-driven ribotoxic stress response (RSR) is activated by ribosome stalling and/or collisions. Recent work demonstrates that RSR also plays a role in innate immunity by activating the human NLRP1 inflammasome. Here, we report that ZAKα and NLRP1 sense bacterial exotoxins that target ribosome elongation factors. One such toxin, diphtheria toxin (DT), the causative agent for human diphtheria, triggers RSR-dependent inflammasome activation in primary human keratinocytes. This process requires iron-mediated DT production in the bacteria, as well as diphthamide synthesis and ZAKα/p38-driven NLRP1 phosphorylation in host cells. NLRP1 deletion abrogates IL-1β and IL-18 secretion by DT-intoxicated keratinocytes, while ZAKα deletion or inhibition additionally limits both pyroptotic and inflammasome-independent non-pyroptotic cell death. Consequently, pharmacologic inhibition of ZAKα is more effective than caspase-1 inhibition at protecting the epidermal barrier in a 3D skin model of cutaneous diphtheria. In summary, these findings implicate ZAKα-driven RSR and the NLRP1 inflammasome in antibacterial immunity and might explain certain aspects of diphtheria pathogenesis.
Topics: Humans; Diphtheria Toxin; Diphtheria; Inflammasomes; Pyroptosis; Immunity, Innate; NLR Proteins
PubMed: 37642997
DOI: 10.1084/jem.20230105 -
The Journal of Infectious Diseases Jun 2022Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This...
BACKGROUND
Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age.
METHODS
In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed.
RESULTS
Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses.
CONCLUSIONS
RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis.
CLINICAL TRIALS REGISTRATION
NCT04071158.
Topics: Adult; Antibodies, Bacterial; Antibodies, Viral; Diphtheria; Diphtheria Toxoid; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Immunogenicity, Vaccine; Middle Aged; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Tetanus; Whooping Cough; Young Adult
PubMed: 34637519
DOI: 10.1093/infdis/jiab505 -
Public Health Action Jun 2023A rising number of diphtheria cases were recorded in Europe in 2022, including in Belgium, within the newly arriving young migrant population. In October 2022, Médecins...
A rising number of diphtheria cases were recorded in Europe in 2022, including in Belgium, within the newly arriving young migrant population. In October 2022, Médecins Sans Frontières (MSF) opened a temporary roadside container-clinic offering free medical consultations. Over 3 months of activity, the temporary clinic detected 147 suspected cases of cutaneous diphtheria with 8 laboratory-confirmed cases growing toxigenic . This was followed by a mobile vaccination campaign, during which 433 individuals living rough in squats and informal shelters were vaccinated. This intervention has shown how even in Europe's capital, access to preventive and curative medical services remains difficult for those who need it the most. Appropriate access to health services, including routine vaccination, are crucial to improve the health status among migrants.
PubMed: 37359068
DOI: 10.5588/pha.23.0011 -
Proteomes Dec 2023Within the genus , six species are potential carriers of the gene, which encodes the highly potent diphtheria exotoxin: , , , , and Based on their potential to infect... (Review)
Review
Within the genus , six species are potential carriers of the gene, which encodes the highly potent diphtheria exotoxin: , , , , and Based on their potential to infect different host species and cause either human infections, zoonotic diseases or infections of economically important animals, these bacteria are of high scientific and economic interest and different research groups have carried out proteome analyses. These showed that especially the combination of MS-based proteomics with bioinformatic tools helped significantly to elucidate the functional aspects of corynebacterial genomes and to handle the genome and proteome complexity. The combination of proteomic and bioinformatic approaches was also used to discover new vaccine and drug targets. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been established as a fast and precise tool for the identification of these bacteria.
PubMed: 38250813
DOI: 10.3390/proteomes12010002 -
Emerging Infectious Diseases Aug 2023Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to... (Review)
Review
Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001-2020. During 2010-2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.
Topics: Adult; Humans; Diphtheria; Japan; Corynebacterium; Corynebacterium Infections; Corynebacterium diphtheriae; Diphtheria Toxin; Diphtheria Toxoid
PubMed: 37486266
DOI: 10.3201/eid2908.220058