Epidemiological contact investigation simulator — from index case identification through concentric-circle prioritization to latent infection testing and treatment linkage
Tuberculosis contact investigations begin the moment a case of active pulmonary or laryngeal TB is reported to public health authorities. These two anatomical forms are the infectious forms of disease — patients cough or speak, generating airborne droplet nuclei (1–5 µm) laden with Mycobacterium tuberculosis that can remain suspended and travel through shared air space. Extrapulmonary disease (lymph node, bone, meningeal) is rarely infectious unless it involves an open, draining lesion. Because every day of delay allows further undetected transmission, public health guidance (CDC, WHO) recommends beginning the investigation within one to three business days of the report reaching the health department.
Tuberculosis is a mandatorily reportable disease in essentially every jurisdiction worldwide. A case triggers contact investigation when it meets specific criteria:
• Pulmonary TB: disease involving lung parenchyma, confirmed by culture, NAAT (Xpert MTB/RIF Ultra), or strong clinical/radiographic suspicion pending confirmation • Laryngeal TB: rare but exceptionally infectious — even brief conversational exposure can transmit • Pediatric cases (under 5, or any age with cavitary/smear-positive disease): trigger a reverse investigation to identify the adult source case, since children rarely transmit • Drug-resistant TB (MDR/RR-TB): investigated with the same urgency, often higher priority, because treatment options for secondary cases are more limited and costly
Extrapulmonary-only disease without airway involvement (isolated lymphadenitis, bone TB, most meningitis) is not considered infectious and typically does not trigger contact tracing, unless there is a co-existing pulmonary component found on chest imaging.
Once a case is reported, the investigation team reviews diagnostic evidence to grade how infectious the patient likely was:
• AFB sputum smear microscopy: graded from scanty/1+ to 4+ based on bacilli seen per high-power field; higher grades correlate with higher bacillary load and higher secondary attack rates among contacts • Culture positivity: confirms viable, replicating organisms; time-to-positivity in liquid culture (e.g., MGIT) is an additional proxy for bacillary burden — faster growth implies a higher starting inoculum • NAAT (GeneXpert MTB/RIF Ultra): rapid confirmation and semi-quantitative bacillary load (very low/low/medium/high), increasingly used for early infectiousness triage while culture is pending • Chest radiography: presence of cavitary lesions is one of the strongest independent predictors of transmission — cavities communicate directly with the airway and contain enormous mycobacterial populations (up to 10⁸–10⁹ organisms per cavity)
Combining smear status and cavitation yields a simple three-tier infectiousness stratification used throughout this simulator: smear-negative, smear-positive, and cavitary disease (highest transmission risk).
Cavitary disease with a high-grade (3+/4+) sputum smear identifies the patients responsible for a disproportionate share of onward transmission — contact investigation resources are triaged toward these index cases first.
Before any contact can be identified, investigators must reconstruct the period during which the index case was actually infectious — the "exposure window." Get the start date wrong and contacts are missed; get the end date wrong and resources are wasted screening people who were never at risk. Because there is no way to directly measure when a patient became infectious, health departments rely on a structured combination of clinical history, standard look-back rules, and treatment response.
The infectious period start date is estimated using whichever of the following gives the longer (more conservative) window:
• Symptom-based estimate: the interview establishes the onset of a chronic cough (≥2–3 weeks), and the infectious period is typically backdated 3 months from that onset for standard cases • Diagnosis-based estimate: if the symptom history is unreliable or asymptomatic disease was found on screening, 3 months before the diagnostic specimen collection date is used instead • Extension for high-burden disease: cavitary disease, smear-positive results of 3+/4+, or a long duration of unexplained symptoms can extend the presumed infectious period to 6–12 months before diagnosis, since heavy bacillary shedding often predates dramatic symptoms • Special populations: immunocompromised patients (HIV co-infection, biologic therapy) can have atypical or blunted symptoms, making the diagnosis date a more reliable anchor than self-reported symptom onset
The infectious period is generally considered to close only when all of the following are satisfied:
• Effective multi-drug therapy has been administered for a minimum of about two weeks • The patient demonstrates clinical improvement — reduced cough, reduced fever • Sputum smear results show a decreasing bacillary grade, ideally with documented smear or culture conversion
Until these criteria are met, the patient (particularly if still smear-positive) is managed with airborne precautions in healthcare settings and asked to limit congregate exposure in the community. The full exposure window — from the estimated start date through the estimated end date — is what defines which time periods, locations, and contacts fall within scope of the investigation.
With the exposure window defined, investigators must decide whom to interview and test — and in what order. Public health TB programs use the concentric circle model, sometimes called the "stone in the pond": exposure to an infectious case radiates outward in intensity like ripples, and investigation resources are allocated to match that gradient, starting at the center and expanding only as evidence of transmission warrants.
The model organizes contacts into concentric rings around the index case, ranked by exposure intensity:
• Ring 1 — household and high-exposure contacts: people sharing a bedroom, household, vehicle, or workplace cubicle with prolonged daily close contact during the infectious period. These contacts are interviewed and tested first, typically within days. • Ring 2 — frequent or moderate-exposure contacts: coworkers in the same room but not immediately adjacent, classmates, regular social contacts with substantial but less intense exposure. • Ring 3 — casual and community contacts: brief or infrequent contact, shared large spaces (places of worship, public transit), generally investigated only if evidence justifies expansion.
Investigation begins at Ring 1 and expands outward only when the secondary infection yield among inner-ring contacts is higher than expected for casual transmission — the "stone in the pond" ripples outward only as far as the data justify.
If testing of Ring 1 household contacts reveals a secondary latent infection rate well above the expected community background rate, the investigation is expanded to Ring 2 and potentially Ring 3 — casual and community contacts. If Ring 1 yield is low and no additional active cases are found, expansion beyond close contacts is usually not warranted.
Ring assignment is not purely proximity-based — it combines several measurable exposure factors:
• Cumulative duration: many programs use a working threshold around 8+ cumulative hours of shared air space during the infectious period to classify a "close contact" • Proximity and enclosure: unventilated, small, or poorly ventilated rooms dramatically increase risk per hour compared with large or well-ventilated spaces • Index case infectiousness grade: the same duration of exposure to a cavitary, smear 4+ case carries substantially higher risk than exposure to a smear-negative case — this is why the infectiousness slider in this simulator directly scales the modeled secondary infection rate • Contact susceptibility: young children, immunocompromised individuals, and other high-risk contacts may be escalated to Ring 1 handling regardless of exposure duration, because progression to severe disease is faster and more likely in this group
Every contact identified through the concentric circle process is offered testing for TB infection. A positive test does not mean active disease — most infected contacts have latent TB infection (LTBI), a contained, asymptomatic, non-infectious state. The evaluation cascade exists specifically to separate the much larger group with latent infection from the smaller group that has progressed to active, infectious disease and needs a completely different treatment pathway.
Two accepted test types detect TB infection, both measuring the immune response to M. tuberculosis antigens rather than the organism itself:
• Tuberculin skin test (TST): intradermal injection of purified protein derivative (PPD); read 48–72 hours later as induration diameter. A result ≥5 mm is considered positive in close contacts (a lower threshold than the general population because pre-test probability of true infection is high). Requires a return visit to read, and prior BCG vaccination can cause false positives. • Interferon-gamma release assays (IGRA — QuantiFERON-TB Gold Plus, T-SPOT.TB): a single blood draw measures interferon-gamma release from T-cells exposed to M. tuberculosis-specific antigens. Not confounded by prior BCG vaccination, requires only one visit, and is increasingly preferred where available.
Because it takes time for the immune system to mount a detectable response, contacts tested very soon after exposure may show a false-negative result — programs re-test initially negative contacts 8–10 weeks after their last exposure (the "window period") before ruling out infection.
A positive TST or IGRA result launches a mandatory evaluation cascade before any treatment decision is made:
1. Symptom screen: cough, fever, night sweats, weight loss, hemoptysis 2. Chest radiograph: mandatory for every test-positive contact, symptomatic or not, to look for infiltrates, cavitation, or lymphadenopathy 3. If the chest radiograph is abnormal or the contact is symptomatic: sputum collection for AFB smear, NAAT, and culture to definitively rule in or rule out active pulmonary disease 4. Only after active disease is excluded is the contact classified as having latent TB infection and offered preventive treatment
This order matters enormously for treatment safety: preventive regimens (isoniazid, rifapentine, rifampin) are not adequate to cure active disease and, given to a patient with unrecognized active TB, risk selecting for drug-resistant organisms through de facto monotherapy or under-treatment.
Never initiate latent TB preventive treatment before active disease has been excluded by chest radiograph (and sputum studies if indicated). Treating unrecognized active disease as latent infection is a recognized driver of acquired drug resistance.
The final stage of a contact investigation converts test results into action: contacts with latent infection are linked to preventive treatment to stop them from ever progressing to active, infectious disease, while any secondary active cases found during the investigation become new index cases in their own right — potentially launching a second-generation investigation around each of them.
Contacts confirmed to have latent TB infection (positive test, normal chest radiograph, no symptoms) are offered treatment to eliminate the small population of dormant bacilli before they can reactivate — without treatment, roughly 5–10% of infected people will progress to active disease over their lifetime, with the highest risk in the first two years after infection.
Modern short-course regimens have dramatically improved on older 6–9 month isoniazid monotherapy:
• 3HP: once-weekly isoniazid plus rifapentine for 12 doses (~3 months), often given as directly observed or self-administered therapy with app-based support — completion rates are substantially higher than longer regimens • 4R: daily rifampin for 4 months — shorter and better tolerated (less hepatotoxicity) than the traditional 9-month isoniazid course • 9H: daily isoniazid for 9 months — still used where rifamycins are contraindicated (e.g., certain drug interactions)
The single greatest determinant of population-level impact is not which regimen is chosen but whether contacts actually complete it — care cascades routinely lose contacts at every step: testing, evaluation attendance, treatment initiation, and treatment completion.
When a contact investigation uncovers a new active TB case — not just latent infection — that person is immediately managed as a new index case:
• They are started on active-disease treatment (standard four-drug regimen pending drug-susceptibility results) • Their own exposure window and contacts are established, restarting the concentric circle process around them • Because they were likely infected by the original index case, their diagnosis is also a signal to reassess whether Ring 2/Ring 3 expansion is warranted around the original source case
This branching, iterative structure is why a single unrecognized infectious TB case can, left unaddressed, seed a chain of transmission spanning households, workplaces, and community venues. The WHO End TB Strategy identifies rapid, systematic contact investigation and preventive treatment linkage as core pillars for interrupting these chains and driving down community-level incidence.
Every secondary active case identified through contact investigation represents a transmission event that preventive treatment of latent infection is specifically designed to prevent in the next generation of contacts — making cascade-of-care completion, not just testing coverage, the true measure of program success.