Pertussis in infants less than 6 months of age and household contacts, Italy, April 2014

Abstract

We report pertussis cases in 4 infants less than 6 months admitted with symptoms compatible with pertussis to the intensive care unit of the Università Cattolica del Sacro Cuore in Rome, April 2014. Realtime PCR confirmed pertussis diagnosis for the 4 infants, 2 of them were cousins, and for the household contacts of 1 of them. Analysis of pertussis toxin, its promoter and pertactin was also performed. First of all, this report emphasizes the need to investigate household contact of infants with pertussis; secondly, to evaluate the selective vaccination of household members of newborns as an effective program to reduce pertussis in infants.

Keywords:

• household contacts
• infant
• Italy
• pertussis
• vaccine

Abbreviations:

• ptxA, subunit S1 of the pertussis toxin
• ptxP, promoter of the pertussis toxin gene
• prn, pertactin

Pertussis is a highly communicable disease, transmitted from patients to close contacts by respiratory droplets. Parents and household contacts are often considered as a primary source of pertussis infection for infants¹ and for those non-immunized against pertussis a risk of severe clinical illness and death has been recognized.^2,3 It is widely shared the need to confirm a suspected pertussis case with a laboratory assay. One of the method of choice is the realtime PCR on nasopharyngeal aspirate or swab able to differentiate among Bordetellae species.⁴

After 2002, the pertussis vaccine started to be offered free of charge by all Italian Regions.⁵ Based on routine surveillance data, Italy is currently a low incidence country and outbreaks or incidence peaks have been rarely reported after the achievement of a high immunization coverage.⁶

Even if it is a vaccine-preventable disease, pertussis is still circulating and the need to study the genotypic variation of the bacterium in terms of gene sequencing of pertussis toxin and pertactin, as the main acellular vaccine components, deserves particular interest for the efficacy of vaccine coverage in the population.^7,8

In this report, 4 pertussis confirmed cases, occurred among infants less than 6 months of age, have been described together with the identification of B. pertussis in household contacts of one of them. Analysis of genotypic variation in the subunit S1 of the pertussis toxin (ptxA), its promoter (ptxP), together with pertactin (prn) genes, was also performed.^9,10 The 4 infants, with suspected pertussis symptoms, 2 of them were cousins, and family members, were investigated for microbiological purposes collecting nasopharyngeal swabs. Clinically patients presented leukocytosis and dyspnea. Case n.1 was a male 45 d old, with 2 d of cough; the case n. Two was a female 4 months old, with cough of more than 20 days; the case n. Three was a male 1 month old, with the sister, mother and the father also positive for pertussis. The case n. Four, cousin of the case n. Three, was not hospitalized and developed cough of about 10 days, with an onset of cough lather than its cousin. Infants were not immunized with acellular pertussis vaccine (DTaP); case n. Two received the first dose of pertussis vaccine 6 d before the onset of symptoms. Patients and household contacts positive for B. pertussis received clarithromycin (15mg/Kg 2 times/day for infants and 500 mg/die for adults).

DNAs were extracted using QIAamp DNA minikit (QiaGEN, Hilden, Germany). Realtime PCR on IS481 and IS1001 using commercial kits (Diagenode Diagnostics, Liège, Belgium; Argene, bioMérieux, Marcy l'Etoile, France) have been used, following the manufacturer's instructions. Samples from adult family members, given the importance to prevent misdiagnosis of B. holmesii as B. pertussis, have been retested with a specie-specific realtime PCR on pertussis toxin S1 promoter.¹¹ Analysis of genotypic variation using the sequence of amplified fragment for ptxA, ptxP and prn,^9,10 was performed only on the 4 samples collected from infants.

The genetic analysis identified ptxA1, ptxP3 and prn2, in all the 4 infants positive for pertussis. This subtype seems to be prevalent in many parts of Europe, as described already for Italy.¹² Generally, young infants are at highest risk for acquiring pertussis. In the same age group, pertussis outbreaks can be difficult to identify because of co-circulation with other respiratory pathogens often occurs.¹² Moreover, household members were responsible for pertussis transmission of infants.¹³

One of the main issue concerning the disease is the resurgence of reported pertussis, as documented in a number of countries with high vaccine coverage.¹⁴

To the best of our knowledge, this is the first recent report on pertussis among infants and household contacts in Italy. Of note, the presence of isolates carrying virulence-associated allelic variants, prn2 and ptxP3, also identified in recent epidemic strains of Australia,¹⁵ Europe¹⁶ and USA.¹⁷ These variants seems to confer increased survival in a highly vaccinated population.¹⁵

Furthermore, we should mention some limits of our study. In particular, our findings were based on few cases and the genotypic variation among household contacts was not performed. Despite this, the report raises a number of considerations regarding the pertussis in infants less than 6 months; in particular, the importance to investigate household contacts of infants with pertussis. As already reported and discussed by others,¹⁸ the selective vaccination of persons in household with a young infant may substantially reduce the disease burden of pertussis by limiting the transmission. Currently, herd immunity need to be increased, maybe introducing a booster dose of pertussis vaccine in the adult age group population in order to protect the most vulnerable people, as the newborns.

Finally, this report adds to the growing body of data that should consider the potential contribution of genetic changes in circulating and emerging of B. pertussis.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

This work was partially supported by the “Progetto CCM, Ministero della Salute, Sorveglianza di laboratorio di infezioni batteriche sottoposte a sorveglianza europea e da agenti di bioterrorismo”, 2013–2014.