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LITERATURE UPDATE


Pertussis: New preventive strategies for an old disease


Di Mattia G, Nicolai A, Frassanito A, Petrarca L, Nenna R, Midulla F. Paediatr Respir Rev. 2019 Feb; 29: 68–73. doi: 10.1016/j.prrv.2018.03.011.


In the last 20 years, despite high vaccination coverage, epidemics of pertussis are occurring in both developing and developed countries. Many reasons could explain the pertussis resurgence: the increasing awareness of the disease, the availability of new diagnostic tests with higher sensitivity, the emergence of new Bordetella pertussis strains different from those contained in the current vaccines, the asymptomatic transmission of B. pertussis in adolescents and adults and the shorter duration of protection given by the acellular pertussis (aP) vaccine. New preventive strategies have


already been implemented, such as booster doses of aP vaccine in adolescents and adults, maternal immunisation during pregnancy and the ‘cocooning’ strategy, but more are still needed. Knowing what is new about this old disease is necessary to reduce its incidence and to protect infants too young to be vaccinated, which have the highest risk of complications and death.


Is the current pertussis incidence only the results of testing? A spatial and space-time analysis of pertussis surveillance data using cluster detection methods and geographically weighted regression modelling


Kauhl B, Heil J, Hoebe CJ, Schweikart J, Krafft T, Dukers-Muijrers NH. PLoS One. 2017 Mar 9; 12 (3): e0172383. doi: 10.1371/journal.pone.0172383. eCollection 2017.


Despite high vaccination coverage, pertussis incidence in the Netherlands is amongst the highest in Europe with a shifting tendency towards adults and elderly. Early detection of outbreaks and preventive actions are necessary to prevent severe complications in infants. Efficient pertussis control requires additional background knowledge about the determinants of testing and possible determinants of the current pertussis incidence. Therefore, the aim of this study is to examine the possibility of locating possible pertussis outbreaks using space-time cluster detection and to examine the determinants of pertussis testing and incidence using geographically weighted regression models.


48 The authors analysed laboratory


registry data including all geocoded pertussis tests in the southern area of the Netherlands between 2007 and 2013. Socio-demographic and infrastructure- related population data were matched to the geocoded laboratory data. The spatial scan statistic was applied to detect spatial and space-time clusters of testing, incidence and test-positivity. Geographically weighted Poisson regression (GWPR) models were then constructed to model the associations between the age-specific rates of testing and incidence and possible population- based determinants.


Space-time clusters for pertussis incidence overlapped with space-time clusters for testing, reflecting a strong relationship between testing and incidence, irrespective of the examined age group. Testing for pertussis itself was overall associated with lower socio-economic status, multi-person households, proximity to primary school and availability of healthcare. The current incidence in contradiction is mainly determined by testing and is not associated with a lower socioeconomic status. Testing for pertussis follows to an extent the general healthcare seeking behaviour for common respiratory infections, whereas the current pertussis incidence is largely the result of testing. More testing would thus not necessarily improve pertussis control. Detecting outbreaks using space-time cluster detection is feasible but needs to adjust for the strong impact of testing on the detection of pertussis cases.


Antimicrobial susceptibility testing of Finnish Bordetella pertussis isolates collected during 2006-2017 Lönnqvist E, Barkoff AM, Mertsola J, He Q. J Glob Antimicrob Resist. 2018 Sep; 14: 12–16.


doi: 10.1016/j.jgar.2018.02.012.


Macrolides, such as azithromycin and erythromycin, are first-line drugs for the (prophylactic) treatment of pertussis. This study aimed to screen for macrolide-, quinolone- or trimethoprim/ sulfamethoxazole (SXT)-resistant strains among Finnish Bordetella pertussis isolates.


Antimicrobial susceptibility testing was performed on 148 B. pertussis strains isolated during 2006-2017. Isolates were analysed by allele-specific PCR for detection of the macrolide resistance-associated mutation A2047G in the 23S rRNA gene. The gyrA gene was sequenced for detection of the A260G mutation associated with


quinolone resistance. For phenotyping, a random selection was made by selecting every third isolate (n=50) to determine the minimum inhibitory concentrations (MICs) for erythromycin and azithromycin by Etest and the inhibition zone size for nalidixic acid (NAL) and SXT by single disk diffusion assay. Neither the macrolide resistance- associated mutation A2047G nor the quinolone resistance-associated mutation A260G was detected in any of the B. pertussis isolates. MICs of azithromycin and erythromycin ranged between 0.016-0.19 μg/mL and 0.016- 0.25 μg/mL, respectively. The size of the inhibition zone surrounding the NAL disk ranged between 22-27 mm in diameter. The inhibition zone surrounding the SXT disk ranged between 24-37 mm in diameter. No isolates resistant to any of the tested antimicrobials were identified. The allele-specific PCR is a simple and useful tool for screening B. pertussis resistance to macrolides. All Finnish isolates tested were susceptible to macrolides, quinolones and SXT.


Pharmacotherapy for Bordetella pertussis infection. I. A synthesis of laboratory sciences. Cimolai N. Int J Antimicrob Agents. 2021 Mar; 57 (3): 106258.


doi: 10.1016/j.ijantimicag.2020.106258.


There is considerable history and practice experience both with laboratory susceptibility testing for Bordetella pertussis and clinical treatment. This two-part narrative review provides a synthesis of the laboratory and clinical sciences as they apply to this bacterium and the clinical consequences of treating infection.


It is generally held that antibiotic susceptibility testing for B. pertussis is not sufficiently standardised, but there has not been an urgent need to consolidate the same given the lack global experience with major resistance profiles. Experience in China, however, has provided concern for high-level macrolide resistance. The nature and frequency of such resistance has raised the bar for reconsideration of susceptibility testing given that first-line treatment may be regionally compromised. Disk diffusion and Etest susceptibility testing can be recommended for screening resistance among individual isolates of B. pertussis and on an ad hoc manner. Disk diffusion, Etest and/ or critical agar dilution testing can be recommended for large-scale studies. Standards for inoculum, growth atmosphere, timing of interpretation, preferred testing media and controls can


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