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Since the publication in 2003 of a model to estimate the disease burden of pertussis, new evidence of the protective effect of incomplete pertussis vaccination against severe pertussis has been reported. We revised the model to provide new estimates of regional and global pertussis cases and deaths for children younger than 5 years. We developed a revised model with data from 2014 to estimate pertussis cases and deaths. Pertussis cases were defined according to the WHO clinical case definition, as a coughing illness lasting at least 2 weeks with paroxysms of coughing, inspiratory whooping, or post-tussive vomiting. We used UN population estimates and WHO and UNICEF data on national pertussis immunisation coverage. Estimates were made for vaccine effectiveness against pertussis cases and deaths for one, two, and three doses of vaccination, probability of infection in low and high coverage countries, and case fatality ratios in low and high mortality countries in two age groups: infants younger than 1 year and children aged 1–4 years. We did sensitivity analyses with a range of input parameters to assess the effect of uncertainty of the input parameters on the model outputs. We estimated that there were 24·1 million pertussis cases and 160 700 deaths from pertussis in children younger than 5 years in 2014, with the African region contributing the largest proportions (7·8 million [33%] cases and 92 500 [58%] deaths). 5·1 million (21%) estimated pertussis cases and 85 900 (53%) estimated deaths were in infants younger than 1 year. In the sensitivity analyses, the estimated number of cases ranged from 7 million to 40 million and deaths from 38 000 to 670 000. Our estimates suggest that, compared with the 1999 estimates published in 2003 (30·6 million pertussis cases and 390 000 deaths from pertussis in children younger than 5 years), the numbers of cases and deaths of pertussis have fallen substantially. Model sensitivity emphasised the importance of better surveillance to improve country-level decision making and pertussis control. None.

Objectives To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A.Design Systematic review, including assessment of risk of bias, and meta-analyses of similar studies.Study eligibility criteria Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5.Data sources Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified.Results Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV.Conclusions Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.

The effectiveness of maternal immunization in preventing infant pertussis was first demonstrated in England, 1 year after the program using diphtheria–tetanus–5-component acellular pertussis–inactivated polio vaccine (dT5aP-IPV) was introduced in 2012. Vaccine effectiveness against laboratory-confirmed pertussis has been sustained >90% in the 3 years following its introduction, despite changing to another acellular vaccine with different antigen composition. Consistent with this, disease incidence in infants <3 months of age has remained low despite high activity persisting in those aged 1 year and older. Vaccine effectiveness against infant deaths was estimated at 95% (95% confidence interval, 79%–100%). Additional protection from maternal immunization is retained in infants who received their first dose of the primary series. There is no longer evidence of additional protection from maternal vaccination after the third infant dose. Although numbers are small and ongoing assessment is required, there is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination.

Background. In the current era, most pertussis deaths occur in infants <3 months of age. Leukocytosis with lymphocytosis and pneumonia are commonly observed among cases of severe pertussis. Methods. Risk factors associated with fatal pertussis were identified by comparing fatal pertussis cases among patients <120 days of age occurring from 1 January 1998 through 26 December 2014, matched by age (<120 days), county of residence, and closest symptom onset date with 1–4 nonfatal hospitalized cases. California Department of Public Health surveillance data were reviewed to identify cases; demographics, clinical presentation, and course were abstracted from corresponding birth and medical records. Logistic regression and classification tree analyses were used to examine the risk of fatal pertussis with respect to identified factors. Results. Fifty-three fatal infant pertussis cases were identified and compared with 183 nonfatal hospitalized pertussis cases. Fatal cases had significantly lower birth weight, younger gestational age, younger age at time of cough onset, and higher peak white blood cell (WBC) and lymphocyte counts. Fatal cases were less likely to have received macrolide antibiotics and more likely to have received steroids or nitric oxide and to develop pulmonary hypertension, seizures, encephalitis, and pneumonia. Additionally, exchange transfusion, extracorporeal membrane oxygenation, and intubation occurred significantly more frequently among fatal cases. In multivariate analyses, peak WBC count, birth weight, intubation, and receipt of nitric oxide were predictors of death. Conclusions. Early recognition of pertussis in young infants and treatment with appropriate antibiotic therapy are important in preventing death. Several risk factors are strongly associated with fatal pertussis in infants.

Five infants died of whooping cough in England in the first three months of 2024. As rates of the disease continue to rise, Jacqui Wise answers some key questions

ObjectivesDescribe clinical characteristics, treatment and outcomes of children treated for life-threatening pertussis in paediatric intensive care units during the 2023–2024 outbreak in Great Britain.DesignNational multi-centre audit.SettingAll paediatric intensive care units (PICUs) in Great Britain.PatientsBetween November 2023 and June 2024, 54 children with a proven diagnosis of Bordetella pertussis as the primary reason for intensive care admission requiring invasive ventilation.InterventionsNone.Main outcome measuresMortality on PICU, length of stay and number of invasive ventilation days.ResultsMedian admission age 43 days, with peak blood white cell count (WCC) from 6×109/L to 149×109/L. 23% of infants’ mothers were vaccinated during pregnancy (national average 59%). Mortality was 11/54 (20%), with 10 in infants <3 months. The survivor with the highest WCC peaked at 82×109/L prior to exchange transfusion (XT), and the highest peak WCC in a survivor without XT was 71×109/L. Eighteen patients underwent 27 XTs for leucoreduction, initiated at median peak WCC of 54×109/L (range 32–148). All who died had XT planned, with nine completing. None with a peak WCC of <51×109/L died, although four patients underwent XTs. In patients with rising WCC, survivors’ rise rate was lower than those who died (0.23×109/L/hour vs 1.4×109/L/hour).ConclusionsIn children invasively ventilated due to Bordetella pertussis, higher peak WCC, rapid WCC rise and a primary admission reason other than apnoeas are associated with mortality. XTs can be avoided in WCC <50×109/L. Maternal vaccination rate was lower in this cohort than the general population.

This study examines the trends in pertussis incidence, mortality, and disability-adjusted life-years (DALYs) among children from 1990 to 2021. Data on pertussis incidence, mortality, and DALYs rates in children were extracted from the Global Burden of Disease (GBD) database, covering 1990–2021 across 204 countries and regions. Children were divided into four age groups: under 1 year, 1–4 years, 5–9 years, and 10–14 years. Data were categorized by age, gender, year, region, and Socio-demographic Index (SDI). The estimated annual percentage change (EAPC) method to assess trends. In 2021, a downward trend was observed in global childhood pertussis incidence, mortality, and DALYs. Over 30 years, global pertussis cases fell by 77.73 % (EAPC -2.62, 95 % Confidence interval [CI] −3.35 to −1.89), deaths by 80.3 % (EAPC -3.24, 95 % CI −3.97 to −2.51), and DALYs by 80.29 % (EAPC −3.24, 95 % CI −3.97 to −2.50). Before the 2020 COVID-19 outbreak, only low SDI regions showed increasing pertussis cases in children. Children under one year had the highest incidence, mortality, and DALYs. Female children generally had higher rates than males. Post-2020, global incidence and mortality rates significantly declined, likely due to COVID-19-related measures. Globally, childhood pertussis incidence, mortality, and DALYs have decreased over 30 years. However, in low SDI regions like Somalia, the pertussis burden remains high, necessitating financial and medical support. Given the high rates among children under one year, vaccination efforts, timely diagnosis, and prevention of complications are crucial.