That persistent, nagging cough that won't go away could be more than just a cold—it might be a disease you thought disappeared in childhood.
You likely think of whooping cough as a childhood illness, a relic of the past that vaccines have largely conquered. Yet, in a quiet but significant shift, adults and adolescents have become the silent carriers of pertussis. For decades, diagnosing it in this group was notoriously difficult—until a groundbreaking study unlocked a hidden world of infection through a simple blood test.
Whooping cough, caused by the bacterium Bordetella pertussis, has been called the "great masquerader" in adolescents and adults. Unlike infants who develop the characteristic "whoop" and severe symptoms, older individuals often experience a persistent, nagging cough that can last for weeks or even months. This makes it easily mistaken for bronchitis, asthma, or just a stubborn cold 1 .
This diagnostic blind spot has serious public health implications. Undiagnosed adults unknowingly become the primary source of infection for vulnerable infants, for whom pertussis can be life-threatening 1 . Solving this diagnostic puzzle became an urgent priority for researchers.
While the bacteria themselves disappear quickly, the human immune system leaves a lasting fingerprint of infection through specific antibodies.
The scientific breakthrough came from an unexpected direction. Researchers realized that while the bacteria themselves disappear quickly, the human immune system leaves a lasting fingerprint of infection through specific antibodies.
The key was identifying which antibodies specifically indicated a recent B. pertussis infection rather than past exposure or vaccination. Among the various proteins the bacteria produce, pertussis toxin (PT) emerged as the ideal candidate 1 .
PT is unique—it's only produced by B. pertussis, meaning antibodies against it provide a specific signature of infection. Unlike other bacterial targets that might cross-react with similar organisms, PT antibodies reliably point to pertussis and nothing else 1 8 .
The pivotal research came from the Third National Health and Nutrition Examination Survey (NHANES III), which analyzed serum samples from over 6,000 U.S. residents aged 6-49 years. This massive dataset provided the first representative picture of pertussis antibody levels across the American population 1 2 .
The scale and design of the NHANES III study made its findings particularly powerful. Researchers employed sophisticated statistical models to distinguish between different exposure groups in the population, essentially separating those with likely recent infection from those with past exposure or vaccination 1 .
The laboratory work was meticulous. Scientists used enzyme-linked immunosorbent assays (ELISAs) to measure immunoglobulin G (IgG) antibodies against three pertussis antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), and fimbria types 2 and 3 (FIM). The tests were standardized against reference sera to ensure consistency across thousands of samples 1 .
A critical finding emerged even before the diagnostic cutoffs were established: measurable anti-FHA and anti-FIM antibodies were common (found in 65% and 62% of people, respectively), but quantifiable anti-PT antibodies were rare, appearing in only 16% of the population 1 . This pattern confirmed that PT antibodies were the most specific indicator of recent infection.
The central challenge was determining what level of anti-PT IgG antibodies should trigger a positive diagnosis. Set the threshold too low, and you get false positives; set it too high, and you miss real cases.
Definitive cutoff for anti-PT IgG antibodies indicating recent pertussis infection
Sensitivity
Specificity
When this cutoff was applied to samples from people with culture-confirmed pertussis, it demonstrated 80% sensitivity (correctly identifying infected individuals) and 93% specificity (correctly ruling out non-infected individuals) 1 .
| Antigen | Percentage with Quantifiable Antibodies (>20 EU) | Significance for Diagnosis |
|---|---|---|
| Pertussis Toxin (PT) | 16% | Highly specific for recent infection |
| Filamentous Hemagglutinin (FHA) | 65% | Less specific, common in population |
| Fimbriae (FIM) | 62% | Less specific, common in population |
| Laboratory/Country | Diagnostic Cutoff | Notes |
|---|---|---|
| NHANES III Study (USA) | ≥94 EU | Primary cutoff with optimal sensitivity/specificity |
| Massachusetts State Laboratory (USA) | 200 EU | More conservative cutoff |
| The Netherlands | 125 EU | Intermediate value |
| Various Other Laboratories | 49-62.5 EU | Suggests possible infection |
| Reagent/Solution | Function in Research | Specific Examples |
|---|---|---|
| Purified Antigens | Coat ELISA plates to capture specific antibodies | PT, FHA, FIM from vaccine manufacturers |
| Reference Sera | Standardize measurements across labs and time | U.S. Reference Pertussis Serum, Human, Lot 3 (HRP3); WHO International Standard |
| Enzyme-Conjugated Antibodies | Detect human antibodies bound to antigens | Horseradish peroxidase-conjugated anti-human IgG |
| Assay Buffers & Substrates | Enable accurate antibody measurement and signal detection | PBS buffers with bovine serum albumin; p-Nitrophenyl phosphate (PNPP) |
| Lyophilized Standards & Controls | Ensure consistent assay performance in every run | Kit standards (15-480 EU/mL); negative, intermediate, and positive controls |
The establishment of the 94 EU cutoff revolutionized pertussis surveillance. For the first time, public health officials had a standardized, reliable tool to confirm pertussis outbreaks using single serum samples from coughing adults 1 6 . This simple ELISA-based approach could be transferred to public health laboratories nationwide, creating a consistent framework for diagnosis 6 .
Culture and PCR tests with limited effectiveness in adults due to timing and bacterial scarcity.
Establishment of anti-PT IgG cutoff (≥94 EU) enabling reliable diagnosis from single serum samples.
Complementary use of PCR for early detection and serology for confirmed diagnosis.
Research into antibody quality and protective capacity against future infections.
Recent studies highlight how advanced PCR testing now complements serological diagnosis, especially in early stages of infection 3 .
The story of pertussis diagnostics continues to evolve. As vaccination strategies change and new vaccines are developed, understanding the immune response they generate remains crucial 7 8 . The establishment of those initial diagnostic cutoff points didn't just help us identify who was sick—it opened a window into the complex relationship between humans and a pathogen that continues to surprise us.
The next time you hear a persistent cough that just won't quit, remember: there's an invisible world of immune responses at work, and thanks to scientific detective work, we now have the tools to decipher its clues.