LITERATURE UPDATE
Quantifying IgG antibodies to pertussis toxin (PT) is the most specific and sensitive method for the serodiagnosis of a Bordetella pertussis infection. Since PT is a component of acellular pertussis vaccines, anti-PT IgG is also induced by vaccination, precluding pertussis serodiagnosis based exclusively on anti-PT IgG in recently vaccinated subjects. Here, the authors aim to identify additional B. pertussis-specific serological markers that can discriminate between infection and recent vaccination.
The clinical usefulness of measuring
Since 2010, members of the CDC Pertussis and Diphtheria Laboratory have conducted training courses in Latin America on laboratory diagnosis of pertussis.
be extrapolated from the publications to date. Such methods should be able to detect high-level resistance to several antibiotics, but especially macrolides. Concern for intermediate-susceptible categories requires consideration as well as the correlation with bacteriological and clinical outcomes. Provisional standards can be applied at this time, and modification or fine-tuning of any such standards are open to future investigation.
Pharmacotherapy for Bordetella pertussis infection. II. A synthesis of clinical sciences Cimolai N. Int J Antimicrob Agents. 2021 Mar; 57 (3): 106257.
doi: 10.1016/j.ijantimicag.2020.106257.
Despite the plethora of studies that have examined laboratory susceptibility testing for Bordetella pertussis, assessments of treatment have lagged far behind both in quality and quantity. Macrolides and trimethoprim/ sulfamethoxazole historically served the needs of both treatment and prevention, albeit there is still controversy about the degree of protection measured both bacteriologically and clinically. As high-level macrolide resistance
has emerged in some geographic regions and since macrolides have been the mainstay of therapy, alternative antibiotics need to be defined for pertussis. In vitro susceptibility testing suggests the potential for several alternatives to macrolides, including
trimethoprim/sulfamethoxazole, specific β-lactam agents, chloramphenicol, some quinolones and possibly some tetracyclines. For the latter antibiotics, more clinical studies for treatment and prophylaxis are required in to order to establish bacteriological-clinical correlates for outcome. In the interim, if the clinical
circumstances mandate the use of proposed interim alternatives to macrolides, outcomes should be assessed with test of cure by culture, since genetic amplification technologies do not discriminate bacterial viability. Whereas there may be debate in regard to using placebo or macrolides as the controls for alternative antibiotic therapy in geographies where most B. pertussis isolates are antibiotic-susceptible, both placebo and macrolide controls should be assessed along with alternative antibiotics in well-designed controlled studies in regions pressured by macrolide resistance. Outcomes of clinical response and epidemiological patterns of disease should continue to be monitored given the degree of macrolide resistance that is emerging.
Assessment of IgA anti-PT and IgG anti-ACT reflex testing to improve Bordetella pertussis serodiagnosis in recently vaccinated subjects Subissi L, Rodeghiero C, Martini H et al. Clin Microbiol Infect. 2020 May; 26 (5): 645.e1-645.e8.
doi: 10.1016/
j.cmi.2019.10.001.
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IgA directed to the vaccine antigen PT and IgG directed to non-vaccine antigens (Fim2/3, LPS, ACT, CatACT) was evaluated in nine well characterised subject groups, aged 10–89 years (n=390). Serum anti-PT IgG levels (>125 IU/mL) served as an indicator for a recent B. pertussis infection. Comparing symptomatic pertussis-infected subjects (n=140) with recently vaccinated, non- infected subjects (n=100) revealed the optimal cut-off, accuracy, sensitivity and specificity for each single parameter. For pertussis diagnosis in recently vaccinated subjects, the measurement of anti-PT IgA (cut-off 15 IU/mL) and anti-ACT IgG (cut-off 15 U/mL) resulted in accuracies of 95% (91.5–97.1) and 87.5% (82.7–91.1), sensitivities of 92.9% (87.4–96.0) and 83.6% (76.5–88.8) and specificities of 98% (93.0–99.4) and 93% (86.3–96.6), respectively. Comparing anti-PT IgA levels between the youngest (10–19 years, n=38) and oldest (70–89 years, n=17) age groups revealed an age-dependent increase in antibody levels in pertussis-infected subjects (P<0.0001).
Reflex testing of anti-PT IgA and anti-ACT IgG improves pertussis serodiagnosis in recently vaccinated symptomatic subjects with elevated anti- PT IgG levels. Furthermore, both markers can discriminate between vaccination and recent infection in pertussis serosurveillance studies.
In Vivo Models and In Vitro Assays for the Assessment of Pertussis Toxin Activity
Hoonakker ME. Toxins (Basel). 2021 Aug 12; 13 (8): 565. doi: 10.3390/toxins13080565.
One of the main virulence factors produced by Bordetella pertussis is pertussis toxin (PTx) which, in its inactivated form, is the major component of all marketed acellular pertussis vaccines. PTx ADP ribosylates Gαi proteins, thereby affecting the inhibition of adenylate cyclases and resulting in
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CDC; Pamela Cassiday, MS, Pertussis and Diphtheria Laboratory
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