Fatal pertussis in infancy, Italy

Outbreaks of pertussis have recently occurred in indus-trialized countries with high vaccination rates such as theUS, Australia and many European countries, involvingparticularly adolescents, adults and young infants.1Thereasons for “resurgence” of pertussis include waning of im-munity from vaccination or natural infection over time, lowcoverage by acellular vaccine, genetic changes inBorde-tella pertussisstrains, greater awareness of the disease,and improved diagnostic ability through the spread use ofnew molecular techniques.2Due to waning of mother’s im-munity over time, transplacental transfer of pertussis anti-bodies is not protective, and infants too young to havecompleted their vaccination schedules are particularlyvulnerable. They have the highest rate of morbidity, hospi-talization, complications, intensive care unit (ICU) admis-sion, and mortality.3The incidence of pertussis deaths among infants indeveloped countries has increased, with very high mortalityrates in those less than 3 months of age.3Surprisingly, a na-tional surveillance study up to 2012 showed that deathsfrom pertussis have not been reported in Italy since2002.4In addition, no death occurred in Tuscany, Italy,over the period 2013e2014, despite a dramatic increasein hospitalization rate (up to 95,7 per 100,000) in infants.5A recent article in this Journal has highlighted theemerging problems associated withB. pertussisinfectionin infants and strategies to ameliorate this.1We report aretrospective chart review of six fatal cases of pertussisin infants recently admitted to three Italian tertiary carepediatric centers. A death attributed to pertussis wasconfirmed if:i)B. pertussiswas isolated by culture or B. pertussis DNA was identified by real-time polymerase chain reaction (RT-PCR) analysis from a clinical or autopsyspecimen; andii) the clinical presentation was compatiblewith pertussis manifestation in infancy. Demographic char-acteristics, personal history, immunization status, clinicalfeatures and ongoing therapy at admission are presentedinTable 1. Laboratory data, microbiological and radiolog-ical findings, the type of intervention during hospital stay,and the outcome are shown inTable 2.All our patients were less than 3 months of age and twoof them had a history of prematurity, which are both riskfactors for the development of fatal pertussis.6Two pa-tients had close household contacts, thus confirming thatthe primary source of pertussis infection in young infantsis family members, especially parents.7Four infants weretoo young to receive vaccination, one had received onlyone dose of DTaP, and delaying vaccination was recommen-ded for the child with severe prematurity. No mother hadreceived either Tdap vaccine within 2 years before or vacci-nation recommendations during the current pregnancy.This unacceptable black hole in the prevention of a poten-tially devastating disease calls for urgent revision of vacci-nation strategies by the Italian Health National System.The diagnosis of pertussis is frequently missed in in-fants.3Indeed, all infants presented with a recent historyof aspecific respiratory symptoms, and bronchiolitis wasinvariably the initial diagnosis. Due to the high risk for hos-pital outbreak resulting from the lack of recognition ofpertussis, physicians should maintain a high index of suspi-cion for such disease especially outside of the bronchiolitisseason, and a systematic use of RT-PCR is strongly recom-mended in young patients hospitalized for acute, unex-plained respiratory symptoms.All infants had increased white blood cells (WBC) countat presentation, a finding that has been invariably reportedin fatal cases of pertussis.6No particular value of leukocy-tosis accurately predicts death or survival, but any rapidrise in the total WBC count over the course of the diseaseshould represent a warning signal. Bilateral pneumoniawas documented in all our cases. Radiology confirmedpneumonia was found frequently in children with pertussisadmitted to ICU.6Pneumonia either at presentation or dur-ing hospital stay should be considered an ominous finding,thus requiring an immediate, intensive care support forthese children.All but one infants developed severe pulmonary hyper-tension (PH), therefore confirming the central role of thiscondition in fatal pertussis. Children with severe pertussisand PH have a poor outcome on conventional oxygenationand have been placed on extracorporeal membraneoxygenation (ECMO) with limited success.3In our series,the rapid and dramatic evolution of clinical conditions didnot allow us to use this intervention. Indeed, a significantnumber of mortalities for pertussis occur very rapidly, giv-ing little time to intervene. Leukodepletion obtained byeither leukofiltration or exchange transfusion has been pro-posed as additional therapy in severe pertussis, but mortal-ity rates are still unacceptably high.8Further studies needto be performed to demonstrate if leukodepletion followingearly ECMO administration may allow for improved success.Despite strenuous therapeutic measures in ICU, includingconventional mechanical ventilation, high frequencyoscillatory ventilation, inotropic support and inhaled nitricoxide, our patients died. Notably, all these interventionshave been significantly associated with mortality in infantswith pertussis admitted to ICU.9New strategies are required to eliminate pertussisdeaths. They include the development of new vaccines,changing timing and number of doses in immunizationsschedules, vaccinating all close contacts of young infantsimmediately after delivery (cocooning), favouring immuni-zation of pregnant women, and vaccination of neonates atbirth.10Maternal immunization during the third trimester ofpregnancy is to be considered the best strategy for infantprotection from pertussis regardless the source of infec-tion.11Despite specific recommendations issued by themain national scientific societies toward maternal pertussisimmunization during pregnancy, no direct action has beentaken by the Italian Health National System so far.Pertussis deaths among infants still represent a majorhealth concern. Physicians should reserve great attentionto the diagnosis of pertussis when they deal with youngchildren with unexplained respiratory symptoms. Effectivestrategies will have to include new immunization interven-tions, improved education about pertussis manifestations inadolescents and adults, greater awareness of the disease inthe community, earlier diagnosis through modern labora-tory techniques, prompt use of antibiotics, and noveltherapeutic approaches in the most severe cases.