In typical pertussis in young infants, the child will appear deceptively well; he or she will have coryza, sneezing, and a mild cough. There is no fever. This progresses to gagging, gasping, eye ...bulging, bradycardia, cyanosis, and vomiting. There is leukocytosis with lymphocytosis and apneic episodes. Deaths relate to leukocytosis, pulmonary hypertension, and pneumonia. The source of pertussis in young infants is most often a family member with cough illness that is not recognized as pertussis. Diagnosis is based on culture/polymerase chain reaction and leukocytosis with lymphocytosis. Treatment depends on macrolide antibiotic therapy and intubation, with assisted ventilation and oxygen. Prevention is based on prophylactic macrolide treatment, immunization starting at 6 weeks of age, and immunization of all pregnant women in the second or third trimester.
Background. All US women are recommended to receive a tetanus, diphtheria, and acellular pertussis (Tdap) vaccine at 27–36 weeks gestation during each pregnancy to reduce the risk of pertussis to ...their infants. The impact of this strategy on severity of disease among infected infants has not been evaluated. Methods. We use a retrospective cohort study design evaluating whether pertussis-infected infants born in 2011–2015 whose mothers received Tdap vaccine during pregnancy had less severe pertussis, resulting in a lower risk of hospitalization or intensive care unit admission compared with infants born to unvaccinated mothers. Results. Infected infants of vaccinated mothers were significantly less likely to be hospitalized and had significantly shorter hospital stays compared with infants born to unvaccinated mothers, after adjustment for chronological and gestational age and receipt of diphtheria and tetanus toxoids and acellular pertussis vaccine. Unadjusted and adjusted vaccine effectiveness for preventing hospitalization among infants with pertussis was 72% (95% confidence interval CI, 49%–85%) and 58% (95% CI 15%–80%), respectively. No infants born to vaccinated mothers required intubation or died of pertussis. Conclusions. Infants with pertussis whose mothers received Tdap during pregnancy had a significantly lower risk of hospitalization and intensive care unit admission and shorter hospital stays. Prenatal Tdap vaccination is a critical strategy for reducing the morbidity and mortality from pertussis.
Abstract
Background
Measles vaccine failure was first described in 1972. Over the next 20 years, vaccine failure was extensively studied, but during the last 25 years few investigations have been ...performed. We describe the clinical characteristics of measles in previously vaccinated and unvaccinated patients in California.
Methods
All confirmed measles cases reported to the California Department of Public Health from 1 January 2000 through 31 December 2015 were reviewed. Clinical characteristics (rates of hospitalization, cough, coryza, conjunctivitis, and fever) were compared between the previously unvaccinated, those who had had 1 dose of vaccine, and those who had had ≥2 doses of measles vaccine.
Results
There were 232 confirmed measles cases in whom vaccination status was verified; 80% were unvaccinated, 9% had had 1 dose of measles vaccine, and 11% had had ≥2 doses of measles vaccine. Subjects who had had ≥2 doses of measles vaccine had lower rates of hospitalization, cough, coryza, conjunctivitis, and fever than subjects who had 1 dose of measles vaccine or who were unimmunized.
Conclusions
Vaccine failure measles cases were less ill than cases that occurred in unvaccinated patients. Nevertheless, these cases still required the same amount of public health effort in tracing contacts as in cases who were unvaccinated.
This is the largest study of the clinical characteristics of measles in previously vaccinated and unvaccinated patients in the 21st century.
Vaccines (killed whole organisms--DTwP) were developed in the 1930s, and their subsequent use beginning in the late 1940s resulted in a 157-fold decrease in the pertussis attack rate 1, 4. Because ...DTwP vaccines contained endotoxin, their use was associated with considerable side effects. There are five possible reasons for the resurgence: 1) genetic changes in B. pertussis; 2) a decrease in vaccine efficacy; 3) a more rapid occurrence of waning immunity; 4) increased recognition and reporting of pertussis; and 5) newer laboratory diagnostic tests. ...although not discussed here, it is my opinion that live vaccines will not provide as good protection as good DTwP vaccines 12. ...I believe a high priority should be given to the development of less reactogenic whole-cell vaccines.
The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting ...pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)
. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
Effective diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines became available in the 1930s, and they were put into routine use in the United States in the 1940s. Their use reduced the ...average rate of reported pertussis cases from 157 in 100 000 in the prevaccine era to <1 in 100 000 in the 1970s. Because of alleged reactions (encephalopathy and death), several countries discontinued (Sweden) or markedly decreased (United Kingdom, Germany, Japan) use of the vaccine. During the 20th century, Bordetella pertussis was studied extensively in animal model systems, and many "toxins" and protective antigens were described. A leader in B pertussis research was Margaret Pittman of the National Institutes of Health/US Food and Drug Administration. She published 2 articles suggesting that pertussis was a pertussis toxin (PT)-mediated disease. Dr Pittman's views led to the idea that less-reactogenic acellular vaccines could be produced. The first diphtheria, tetanus, pertussis (DTaP) vaccines were developed in Japan and put into routine use there. Afterward, DTaP vaccines were developed in the Western world, and definitive efficacy trials were carried out in the 1990s. These vaccines were all less reactogenic than DTwP vaccines, and despite the fact that their efficacy was less than that of DTwP vaccines, they were approved in the United States and many other countries. DTaP vaccines replaced DTwP vaccines in the United States in 1997. In the last 13 years, major pertussis epidemics have occurred in the United States, and numerous studies have shown the deficiencies of DTaP vaccines, including the small number of antigens that the vaccines contain and the type of cellular immune response that they elicit. The type of cellular response a predominantly, T2 response results in less efficacy and shorter duration of protection. Because of the small number of antigens (3-5 in DTaP vaccines vs >3000 in DTwP vaccines), linked-epitope suppression occurs. Because of linked-epitope suppression, all children who were primed by DTaP vaccines will be more susceptible to pertussis throughout their lifetimes, and there is no easy way to decrease this increased lifetime susceptibility.
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