HomeTreatment of TB disease quickly reduces infectivity and is thus a fundamental component of TB public health management.1–4 Just how quickly people with TB become non-infectious after initiating effective therapy, and what biomarkers best predict this, remains controversial.5,6
A recent systematic review commissioned by the World Health Organization (WHO) to inform the 2019 WHO TB infection Control Guidance update did not find definitive clinical data on the precise number of days or weeks of treatment required to render all people with TB non-infectious. As a result, WHO could not provide explicit guidance on safe timing of patient de-isolation.1,7
Perhaps reflecting the lack of definitive data, infection control guidelines on de-isolation from low-burden countries vary and often equivocate in their specific recommendations6 (see Table 1).
Table 1. Summary of infection control guidance documents from low-incidence countries.
| Country/Organization | Publication | Year | Type of pulmonary TB | Recommendation for de-isolation (provided clinical response is documented, patient is receiving and tolerating a treatment regimen likely to be effective, and drug-resistance is not present) | Reference |
|---|---|---|---|---|---|
| United States of America | Morbidity and Mortality Weekly Report: Hospital Infection Control Guidelines | 2005 | Smear-positive | Minimum 2 weeks and 3 sputum samples are smear-negative | Jensen et al. 9 |
| Smear-negative | Minimum 2 weeks of treatment | ||||
| MDR-TB | Until sputum culture conversion on treatment documented | ||||
| Europe | European Respiratory Society/ European Centre for Disease Prevention and Control Statement: European Union standards for tuberculosis care | 2017 | Smear-positive | Until sputum smear conversion on treatment achieved (Standard 20) | European Centre for Disease Prevention and Control 43 |
| Europe | Reducing tuberculosis transmission: a consensus document from the World Health Organization (WHO) Regional Office for Europe | 2019 | All patients | Sputum smear status should not be used to guide de-isolation. However, specific guidance on duration of infectious cannot be made. | Migliori et al. 5 |
| WHO | WHO guidelines on tuberculosis infection prevention and control: 2019 Update |
2019 | All patients | No specific duration of isolation or parameter provided. Guidelines state that “deisolation should be based on the likely infectivity of the individual case and the availability of other supportive systems (in particular, decentralized models of care)” | Christof et al. 1 |
| United Kingdom | The National Institute for Health and Care Excellence Tuberculosis: management and infection control in hospital | 2020 | Drug-susceptible, pulmonary TB, regardless of smear-status | Consider de-isolation after 2 weeks of therapy if rifampin-resistance is not suspected and treatment response well-documented. | NICE 44 |
| New Zealand | Guidelines for Tuberculosis Control in New Zealand | 2019 | Drug-susceptible cases | “A pragmatic approach may be to isolate cases of pulmonary TB until the full susceptibility results are back from the laboratory. This would mean that most patients are in airborne isolation for up to two weeks, by which time infectivity of even heavily smear-positive patients will have fallen to negligible levels.” “Default de-isolation occurs at two weeks” in hospitalized patients. | Ministry of Health 45 |
| Australia | Infection control guidelines for the management of patients with suspected or confirmed pulmonary tuberculosis in healthcare settings | 2016 | Drug-susceptible cases | “Should remain isolated in a negative pressure room with airborne precautions applied until criteria are met. In principle these criteria should include: a reduction in or absence of cough; reduced smear burden or smear negativity; assured treatment by direct observation; and an appropriate discharge plan. | Coulter and National Tuberculosis Advisory Committee 46 |
Until 1990, prior to the dual threats of human immunodeficiency virus (HIV) and multidrug-resistant (MDR-TB), the “2-week rule” was common practice and guided duration of isolation for people with pulmonary TB post-treatment initiation.8 This rule was informed by human-to-guinea pig studies and observational clinical data. However, in 1994, following high-profile nosocomial MDR-TB outbreaks, the Centers for Disease Control and Prevention changed tack to recommend continuing isolation until at least sputum smear conversion was achieved (demonstrated by 3 consecutive negative sputum samples on microscopy).9 The requirement to confirm bacteriologic response helped to avoid premature de-isolation of patients with unrecognized MDR-TB. Bacteriologic response, usually expressed as sputum smear conversion, following TB treatment start is now a commonly used convention to guide de-isolation and has been incorporated into many recent TB and Infection and Prevention Control guidelines (see Table 1).
However, sputum smear conversion in response to treatment can take weeks, even in drug-susceptible cases, and can prolong duration of isolation significantly.10 In a systematic review of 8 clinical studies, more than 50% of people with pulmonary TB remained smear-positive 3 weeks into treatment and 20% remained smear-positive for more than 2 months.7 Sputum culture conversion on treatment can take even longer (40 days median). Up to 40% of initially smear-positive cases will remain culture positive after 2 months of effective treatment. Thus, these patients were presumably still excreting culturable bacilli for weeks after isolation precautions were lifted.
Against the current convention to isolate until sputum smear conversion, there are several lines of evidence suggesting that people with pulmonary TB may be non-infectious (or at least minimally infectious) very soon after initiation of effective treatment and long before smear conversion is achieved. And, although degree of infectiousness prior to treatment start correlates with sputum smear positivity,11 there is evidence that relative contagiousness, once on TB treatment, is no longer predicted by sputum smear status or culture status.
The evidence-base used to examine these questions can be classified into the following groups: observation of people on treatment and subsequent rates of transmission to contacts, human-to- guinea pig exposure experiments, direct measurements of viable bacilli in patient-produced aerosols, in vitro early bactericidal assays and studies assessing the potential harms of prolonged isolation.
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