Rising pertussis cases and deaths in China: current trends and clinical solutions.

Pertussis, an acute respiratory infection caused by Bordetella pertussis, has recently experienced a dramatic increase in incidence and associated deaths in China, drawing significant clinical attention. This article retrospectively analyzes national data on pertussis incidence and mortality from 2010 to 2024, exploring potential factors contributing to this trend. It also discusses strategies for enhancing vaccination programs, improving early diagnosis and treatment, and optimizing the clinical management of high-risk infants, with the aim of addressing the challenges posed by the current pertussis epidemic.

Attack Rate, Case Fatality Rate and Predictors of Pertussis Outbreak During Pertussis Outbreak Investigation in Ethiopia: Systematic Review and Meta-Analysis.

BACKGROUND: Pertussis, a highly contagious, vaccine-preventable respiratory infection caused by Bordetella pertussis, is a leading global public health issue. Ethiopia is currently conducting multiple pertussis outbreak investigations, but there is a lack of comprehensive information on attack rate, case fatality rate, and infection predictors. This study aimed to measure attack rates, case fatality rates, and factors associated with pertussis outbreak. METHODS: This study conducted a systematic review and meta-analysis of published and unpublished studies on pertussis outbreaks in Ethiopia from 2009 to 2023, using observational study designs, using the guideline Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The study utilized databases like Science Direct, MEDLINE/PubMed, African Journals Online, Google Scholar and registers. The data were collected using an Excel Spreadsheet and then exported to STATA version 17 for analysis. Subgroup analysis was conducted to identify potential disparities. A random effects model was used to consider heterogeneity among studies. I2-squared test statistics were used to assess heterogeneity. The attack rate, case fatality rate, and odds ratio (OR) were presented using forest plots with a 95% confidence interval. Egger's and Begg's tests were used to evaluate the publication bias. RESULTS: Seven pertussis outbreak investigations with a total of 2824 cases and 18 deaths were incorporated. The pooled attack and case fatality rates were 10.78 (95% CI: 8.1-13.5) per 1000 population and 0.8% (95% CI: 0.01-1.58%), respectively. The highest and lowest attack rates were in Oromia (5.57 per 1000 population and in the Amhara region (2.61 per 1000 population), respectively. Predictor of pertussis outbreak were being unvaccinated [odds ratio (OR) = 3.05, 95% CI: 1.83-4.27] and contact history [OR = 3.44, 95% CI: 1.69-5.19]. CONCLUSION: Higher and notable variations in attack and case fatality rates were reported. Being unvaccinated and having contact history were the predictors of contracting pertussis disease in Ethiopia. Enhancing routine vaccination and contact tracing efforts should be strengthened.

Risk factors associated with death in infants <120 days old with severe pertussis: a case-control study.

BACKGROUND AND PURPOSE: Pertussis is a serious infectious disease in young infants, and severe cases frequently cause death. Our study explored risk factors for death from severe pertussis. METHOD: A case-control study of infants with severe pertussis admitted to the paediatric intensive care unit (PICU) in the Children's Hospital of Chongqing Medical University, China, from January 1, 2013, to June 30, 2019, was conducted. Pertussis was confirmed by clinical features and laboratory examinations. Severe pertussis was defined as patients with pertussis resulting in PICU admission or death. To understand the risk factors for death, we compared fatal and nonfatal cases of severe pertussis in infants aged < 120 days by collecting clinical and laboratory data. RESULTS: The participants included 63 infants < 120 days of age with severe pertussis. Fifteen fatal cases were confirmed and compared with 44 nonfatal severe pertussis cases, Four patients with termination of treatment were excluded. In the univariate analysis, the risk factors associated with death included apnoea (P = 0.001), leukocytosis (white blood cell (WBC) count≥30 × 109/L (P = 0.001) or ≥ 50 × 109/L (P = 0)), highest lymphocyte count (P = 0), pulmonary hypertension (P = 0.001), and length of PICU stay (P = 0.003). The multivariate analysis revealed that apnoea (OR 23.722, 95%CI 2.796-201.26, P = 0.004), leukocytosis (OR 63.708, 95%CI 3.574-1135.674, P = 0.005) and pulmonary hypertension (OR 26.109, 95%CI 1.800-378.809, P = 0.017) were significantly associated with death. CONCLUSION: Leukocytosis and pulmonary hypertension exhibited the greatest associations with death in infants with severe pertussis admitted to the PICU. Vaccination is still the most effective protection method against pertussis.

Factores de mortalidad en niños con tosferina maligna / Mortality risk factors in children with severe pertussis

INTRODUCCIÓN: La hiperleucocitosis y la hipertensión pulmonar son factores de riesgo de mortalidad en niños con tosferina maligna. Las opciones terapéuticas disponibles para estos casos graves no se encuentran bien establecidas. Población y métodos: Se diseñó un estudio ambispectivo que incluía a niños diagnosticados de tosferina ingresados en una Unidad de Cuidados Intensivos Pediátricos (UCIP) de un hospital de tercer nivel en España entre enero de 2007 y octubre de 2015. Se compararon variables clínicas y demográficas entre el grupo de niños que sobrevivieron (grupo de supervivientes [GS]) y los que finalmente fallecieron (grupo exitus [EG]). RESULTADOS: Se identificaron un total de 31 pacientes. La mortalidad global fue del 19% (6/31 pacientes). Cinco niños fueron diagnosticados de hipertensión pulmonar. Cinco de seis niños que finalmente fallecieron precisaron canulación en oxigenación por membrana extracorpórea (ECMO). Ocho pacientes recibieron terapia mediante exanguinotransfusión (ET). La mediana de leucocitos antes de la realización de ET fue mayor (81.300 cél./μL) en EG que en GS (57.400 cél./μL), p= 0,05. Los pacientes que fallecieron tuvieron un mayor recuento pico de leucocitos totales, linfocitos, neutrófilos y niveles de proteína C reactiva (PCR) que los niños que sobrevivieron. Las variables que se identificaron como factores de riesgo de mortalidad fueron: una frecuencia cardiaca mayor de 170 lpm (OR 18; IC del 95%: 1,7-192,0), la presencia de neumonía (OR 16,5; IC del 95%: 1,7-165) y la presencia de hipertensión pulmonar (OR 179,6 [6,4-5.027]). CONCLUSIÓN: El uso de variables sencillas como la frecuencia cardiaca, el recuento total de leucocitos o los valores de PCR pueden servir para identificar de forma precoz a pacientes con riesgo de hipertensión pulmonar y tosferina maligna, de forma que procedimientos invasivos como la ET puedan utilizarse de una forma más precoz

BACKGROUND: Hyperleukocytosis and pulmonary hypertension are risk factors for death in infants with severe pertussis. Treatment options in severe pertussis are not well-established. METHODS: We designed an ambispective study of children with pertussis admitted to the pediatric intensive care unit (PICU) of a tertiary level hospital in Spain from January 2007 to October 2015. Clinical and demographical variables were compared between the group of children who survived (survivors group or SG) and those children who died (exitus group or EG). RESULTS: Thirty-one children were identified. Overall mortality rate was 19% (6/31 patients). Five children had pulmonary hypertension. Five out of 6 infants who eventually died had been placed on ECMO. Eight infants needed exchange transfusion (ET). Median leukocyte count immediately before exchange transfusion was higher (81300 cél./μL) in EG than in SG (57400 cél./μL), p= 0.05. Children who died had higher peak values in white blood cell counts (WBC), lymphocyte count, neutrophil counts and PCR levels than children who survived. The following variables were associated with risk of death: a heart rate above 170 bpm (OR 18, CI 95%: 1.7-192,0), the presence of pneumonia (OR 16.5, CI 95%: 1.7-165) and pulmonary hypertension (OR 179,6 [6,4-5027]. CONCLUSION: Early identification of patients at risk for pulmonary hypertension and fatal pertussis using heart rate, WBC and PCR levels would be appropriate so that invasive procedures such as exchange transfusion could be carried out precociously

Clinical Profile of Critical Pertussis in Children at a Pediatric Intensive Care Unit in Northern India.

OBJECTIVE: To delineate the clinical profile, complications, intensive care needs, and predictors of mortality in children with critical pertussis. METHODS: Retrospective analysis of case records of children in the pediatric intensive care unit of a tertiary-care hospital, with a diagnosis of critical pertussis over 3 years. Diagnostic criteria included CDC case definition and confirmation by polymerase chain reaction (PCR), when available. Survivors and non-survivors were compared to identify predictors of mortality. RESULTS: 36 records were analysed, most cases were infants (31, 86.1%). 10 (27.7%) were (below 6 weeks of age). In the rest, 16 (61.5%) were partially immunized or unimmunized against pertussis. Rapid breathing (88.9%), paroxysmal cough (86.1%) and apnea (41.7%) were common presenting complaints. Hypoxemia (97.2%), hyperleukocytosis (61.1%) and encephalopathy (52.8%) were common complications. Intensive care needs were mechanical ventilation in 11 (30.6%), vasoactive support in 7 (19.4%) and exchange transfusion in 3 (8.3%). Female gender, apnea, hyperleukocytosis, encephalopathy, need for vasoactive support, and mechanical ventilation predicted mortality. CONCLUSIONS: Pertussis demands attention due to its varied presentation, increased complications and higher mortality.

Burden of Children Hospitalized With Pertussis in Canada in the Acellular Pertussis Vaccine Era, 1999-2015.

BACKGROUND: Recent increases in pertussis morbidity and mortality rates among young infants have led to a recommendation in some countries for vaccination against pertussis during pregnancy. Having data on the burden of pediatric pertussis in a large population over time is important for establishing the true burden of disease in the acellular pertussis (aP) vaccine era. Here, we describe age-specific epidemiology and morbidity and mortality rates in children hospitalized with pertussis over 17 years across Canada in the aP vaccine era. METHODS: Patients aged ≤16 years who were admitted to 1 of 12 pediatric tertiary-care hospitals across Canada between 1999 and 2015 with confirmed (laboratory-confirmed or epidemiologically linked) or probable (clinically diagnosed) pertussis were included. RESULTS: Overall, 1402 patients with pertussis were included. Infants aged <2 months had the highest mean annual incidences of pertussis hospitalization and intensive care unit (ICU) admission (116.40 [95% confidence interval (CI), 85.32-147.49] and 33.48 [95% CI, 26.35-40.62] per 100 000 population, respectively). The overall proportion of children who required ICU admission was 25.46%, and the proportion was highest in infants aged <2 months (37.90%). Over the span of this study, 21 deaths occurred. Age of <16 weeks, prematurity, encephalopathy, and a confirmed pertussis diagnosis were independent risk factors for ICU admission. Age of <4 weeks, prematurity, and female sex were independent risk factors for death. CONCLUSIONS: In the aP vaccine era, endemic pertussis still contributes considerably to childhood morbidity and death, particularly in infants aged <2 months. Vaccination against pertussis during pregnancy has the potential to reduce this disease burden.

Pertussis epidemiological pattern and disease burden in Brazil: an analysis of national public health surveillance data.

Objective: We described pertussis epidemiological trends in Brazil between 2010 and 2015. We also assessed tetanus, diphtheria and acellular pertussis (Tdap) vaccine coverage among pregnant women from 2014, the year of the introduction of Tdap maternal immunization recommendation in Brazil, to 2016.Methods: Epidemiological data for incidence, prevalence, hospitalization, mortality, and maternal vaccination coverage were calculated based on the Brazilian public surveillance databases.Results: The epidemiological data analysis results showed that the pertussis average incidence rate (IR) was 2.19/100,000 inhabitants for all ages, with a peak in 2014 (4.03/100,000 inhabitants) and highest incidence in <1-year-old children (IR = 175.20/100,000). 97.6% of pertussis deaths (405/415) were in <1-year-old children. Maternal immunization coverage was 9.2% in 2014, 40.4% in 2015, and 33.8% in 2016.Conclusions: Pertussis incidence and pertussis-related deaths increased in Brazil from 2010 to 2014 and decreased in 2015. In the two years, 2015 and 2016 that followed the NIP recommendation, Tdap vaccination coverage of pregnant women was low and varying from region to region. More efforts and national plans would help increase awareness and maternal immunization coverage.

Vaccine-driven virulence evolution: consequences of unbalanced reductions in mortality and transmission and implications for pertussis vaccines.

Many vaccines have heterogeneous effects across individuals. Additionally, some vaccines do not prevent infection, but reduce disease-associated mortality and transmission. Both of these factors will alter selection pressures on pathogens and thus shape the evolution of pathogen virulence. We use a mathematical modelling framework to show that (i) the balance of how vaccines reduce transmission versus mortality and (ii) individual variability in protection conferred both shape the evolution of pathogen virulence. Epidemiological (burden of disease) and evolutionary (pathogen virulence) outcomes are both worse when vaccines confer smaller reductions in transmission than in mortality. Furthermore, outcomes are modulated by variability in vaccine effects, with increased variability limiting the extent of virulence evolution but in some cases preventing eradication. These findings are pertinent to current concerns about the global resurgence of pertussis and the efficacy of pertussis vaccines, as the two classes of these vaccines may reduce disease symptoms without preventing infection and differ in their ability to reduce transmission. Furthermore, these findings point to the importance of generating precise predictions for virulence evolution in Bordetella pertussis (and other similar pathogens) by incorporating empirical characterizations of vaccine effects into models capturing the epidemiological details of this system.

Paediatric hospitalizations due to whooping cough in Spain (1997-2017).

This epidemiological survey estimates the burden of whooping cough in infants up to 12 months old in Spain during a twenty-one-year period (1997-2017). The survey was conducted by reviewing data from the Spanish Surveillance System for Hospital Data. All hospitalizations due to whooping cough for infants, reported during the 1997-2017 period, were analysed. Codes were selected from the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes 033.0-033.9. To explore the latest national outbreak and the implementation of vaccination in pregnant women, analyses were stratified to compare the following periods: 1997-2010, 2011-2015 and 2016-2017. A total of 13,352 hospital discharges for whooping cough in infants up to 12 months old were reported. A total of 6850 discharges in the period 1997-2010, 5271 in the period 2011-2015 and 1231 in 2016-2017 were identified. The annual hospitalization rate prior to 2011 was 131.02 cases per 100,000 infants; in 2011-2015, the rate was significantly higher (250.13 cases per 100,000 infants) and in 2016-2017 it decreased (157.69 cases per 100,000 infants). Most of the cases (n = 11,446) occurred in infants under 4 months of age, with hospitalization rates of 328.80, 670.81 and 385.84 cases per 100,000 infants up to 4 months of age in the periods 1997-2010, 2011-2015 and 2016-17, respectively. Thirty-four deaths occurred in the period 1997-2010, 36 in the period 2011-2015 and 4 in 2016-2017. All of the deaths occurred in infants under 4 months old. The case fatality rate did not vary significantly across the study periods. Whooping cough infections concentrate in infants up to 4 months of age in Spain. Public health measures such as vaccination of pregnant women, caregivers, health care professionals and relatives, especially young parents, could reduce the hospitalization burden during the current outbreak.

The prevention of severe pertussis and pertussis deaths in young infants.

INTRODUCTION: Today, in the developed world, virtually all deaths due to Bordetella pertussis illnesses occur in young infants. Areas Covered: Pertussis in young infants is characterized by an afebrile cough illness with coryza, apnea, seizures, cyanosis, and emesis. Severe illness is associated with high leukocyte and lymphocyte counts, rapid respiratory and cardiac rates and pneumonia. Many routine intensive care treatment procedures are detrimental: these include steroids and nitric oxide. Preventative measures include: quarantine, prophylactic antimicrobial agents and immunizations of the mother to be with Tdap between 27 and 36 weeks gestation. Expert Opinion: Infants deaths are due to the irreversible pulmonary hypertension which is caused by aggregates of leukocytes in the small vessels in the lung. The leukocytosis with lymphocytosis is due to pertussis toxin. It can be treated by exchange blood transfusions. However for this to be successful it needs to be started before shock or organ failure has occurred. To prevent pertussis in young infants, attention needs to be directed to the diagnosis and treatment of pertussis in adolescents and adults. Also important are antimicrobial prophylaxis in the infant and the immunization of mothers to be with Tdap vaccine during all pregnancies.

Severe Pertussis Infections in the United States, 2011-2015.

BACKGROUND: The incidence of pertussis in the United States has increased in recent years. While characteristics of severe pertussis infection have been described in infants, fewer data are available in older children and adults. In this analysis, we characterize pertussis infections in hospitalized patients of all ages. METHODS: Cases of pertussis with cough onset from 1 January 2011 through 31 December 2015 from 7 US Emerging Infections Program Network states were reviewed. Additional information on hospitalized patients was obtained through abstraction of the inpatient medical record. Descriptive and multivariable analyses were conducted to characterize severe pertussis infection and identify potential risk factors. RESULTS: Among 15942 cases of pertussis reported, 515 (3.2%) were hospitalized. Three hospitalized patients died. Infants aged <2 months accounted for 1.6% of all pertussis cases but 29.3% of hospitalizations. Infants aged 2-11 months and adults aged ≥65 years also had high rates of hospitalization. Infants aged <2 months whose mothers received acellular pertussis during the third trimester and children aged 2 months to 11 years who were up to date on pertussis-containing vaccines had a 43%-66% reduced risk of hospitalization. Among adolescents aged 12-20 years, 43.5% had a history of asthma, and among adults aged ≥65 years, 26.8% had a history of chronic obstructive pulmonary disease. CONCLUSIONS: Individuals at the extreme ends of life may be the most vulnerable to severe pertussis infections, though hospitalization was reported across all age groups. Continued monitoring of severe pertussis infections will be important to help guide prevention, control, and treatment options.

Pertussis in Poland in 2016

INTRODUCTION: In Poland, the high incidence of pertussis has been maintained for 10 years ­ in 2016 it was 17,77 per 100,000 population and it was 38% more compared to the previous year. The high percentage of pertussis is still present in those who are older, who may be a source of infection for non-immunized or not fully immunized newborns and infants. The most effective prevention strategy remains the implementation of vaccinations in accordance with the current calendar. OBJECTIVES: The aim of the article is to assess the epidemiological situation of pertussis in Poland in 2016 compared to the situation in previous years, with particular emphasis on the assessment of the status of inoculation of children against pertussis. MATERIALS AND METHODS: Analysis of the epidemiological situation of pertussis in Poland was carried out on the basis of individual reports of suspected cases of pertussis sent to NIZP-PZH by regional sanitaryepidemiological stations, data from the bulletin "Infectious diseases and poisoning in Poland in 2016"(2) and the bulletin "Protective vaccinations in Poland in 2016"(3). RESULTS: In 2016, 6 828 cases of pertussis were registered. The incidence was 17.77 per 100,000 population and was 38% higher compared to the previous year (12.89). The highest incidence of pertussis occurred in people aged 10-14 (88.1), and high in children aged 0 and 3 years - 76.7 and 77.0 per 100,000 population. Of the 6 828 patients with pertussis, 1 640 people were hospitalized (24% of total). In 2016, no deaths were reported due to pertussis. SUMMARY AND CONCLUSIONS: The increase in pertussis observed in 2016 indicates the persistent circulation of bacteria in the environment and still persistent population sensitivity to infection. The only effective strategy to reduce the number of cases remains the use of vaccinations according to the current calendar and recommendations of experts.

Vaccine-preventable child deaths in New South Wales from 2005 to 2014: How much is preventable?

AIM: To identify and describe potentially vaccine-preventable child deaths in New South Wales (NSW). METHODS: Child deaths in NSW from 2005 to 2014 potentially preventable by vaccination were identified from the NSW Child Death Register (maintained by the NSW Ombudsman) and the Notifiable Conditions Information Management System (NSW Health). Medical and post-mortem records were reviewed. Cases were classified as vaccine-preventable based on the strength of evidence for the relevant infection causing death and likelihood that death was preventable through vaccination. A two-source capture-recapture method was used to estimate the true number of deaths. Age-specific mortality rate and number of deaths by disease, area of residence and comorbidity were analysed. Deaths were classified as preventable based on vaccine availability, eligibility under the National Immunisation Program, age and presence of any contraindications. RESULTS: Fifty-four deaths were identified as definitely or probably due to diseases for which a vaccine was available, with a total average annual mortality rate of 0.33 per 100 000 children and 2.1 per 100 000 infants. Two thirds of deaths occurred in children with no identified comorbidities. Twenty-three deaths were classified as preventable or potentially preventable by vaccination, with influenza (12 deaths) and meningococcal disease (five deaths) most common. An additional 15 deaths would be potentially preventable as of August 2016 due to immunisation recommendation changes including maternal vaccination. CONCLUSION: Maternal vaccination along with increased uptake of childhood influenza vaccination could reduce child deaths, particularly from influenza.

Extracorporeal Membrane Oxygenation for Pertussis: Predictors of Outcome Including Pulmonary Hypertension and Leukodepletion.

OBJECTIVE: The recent increase of pertussis cases worldwide has generated questions regarding the utility of extracorporeal membrane oxygenation for children with pertussis. We aimed to evaluate factors associated with extracorporeal membrane oxygenation outcome. DESIGN: The study was designed in two parts: a retrospective analysis of the Extracorporeal Life Support Organization Registry to identify factors independently linked to outcome, and an expanded dataset from individual institutions to examine the association of WBC count, pulmonary hypertension, and leukodepletion with survival. SETTING: Extracorporeal Life Support Organization Registry database from 2002 though 2015, and contributions from 19 international centers. PATIENTS: Two hundred infants from the Extracorporeal Life Support Organization Registry and expanded data on 73 children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 200 infants who received extracorporeal membrane oxygenation for pertussis, only 56 survived (28%). In a multivariable logistic regression analysis, the following variables were independently associated with increased chance of survival: older age (odds ratio, 1.43 [1.03-1.98]; p = 0.034), higher PaO2/FIO2 ratio (odds ratio, 1.10 [1.03-1.17]; p = 0.003), and longer intubation time prior to the initiation of extracorporeal membrane oxygenation (odds ratio, 2.10 [1.37-3.22]; p = 0.001). The use of vasoactive medications (odds ratio, 0.33 [0.11-0.99]; p = 0.047), and renal neurologic or infectious complications (odds ratio, 0.21 [0.08-0.56]; p = 0.002) were associated with increased mortality. In the expanded dataset (n =73), leukodepletion was independently associated with increased chance of survival (odds ratio, 3.36 [1.13-11.68]; p = 0.03) while the presence of pulmonary hypertension was adverse (odds ratio, 0.06 [0.01-0.55]; p = 0.01). CONCLUSIONS: The survival rate for infants with pertussis who received extracorporeal membrane oxygenation support remains poor. Younger age, lower PaO2/FIO2 ratio, vasoactive use, pulmonary hypertension, and a rapidly progressive course were associated with increased mortality. Our results suggest that pre-extracorporeal membrane oxygenation leukodepletion may provide a survival advantage.