Heterogeneity in tuberculosis transmission and the role of geographic hotspots in propagating epidemics

Dowdy, David W.; Golub, Jonathan E.; Chaisson, Richard E.; Saraceni, Valéria

doi:10.1073/pnas.1203517109

Cited by 131 publications

(125 citation statements)

References 26 publications

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“…Per-test outlay of constrained resources ('unit cost') potential importance of the late symptomatic stage when the rate of diagnosis is diminished. Here, transmission in the late symptomatic stage is sufficiently strong for 55% of the transmission load to occur from a high-risk (and symptomatic) subgroup that accounts for no more than 10% of the total population -a level of disproportionate transmission that is only modestly higher than has been suggested in some settings 65 . Figure 4 shows results for the incremental value (Equation 1), comparing diagnostic tests that target different stages and under different transmission scenarios.…”

Section: Box 1 | Estimating the Incremental Value Of Tuberculosis Diamentioning

confidence: 85%

Understanding the incremental value of novel diagnostic tests for tuberculosis

Arinaminpathy

Dowdy

2015

Nature

109

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Tuberculosis is a major source of global mortality caused by infection, partly because of a tremendous ongoing burden of undiagnosed disease. Improved diagnostic technology may play an increasingly crucial part in global efforts to end tuberculosis, but the ability of diagnostic tests to curb tuberculosis transmission is dependent on multiple factors, including the time taken by a patient to seek health care, the patient's symptoms, and the patterns of transmission before diagnosis. Novel diagnostic assays for tuberculosis have conventionally been evaluated on the basis of characteristics such as sensitivity and specificity, using assumptions that probably overestimate the impact of diagnostic tests on transmission. We argue for a shift in focus to the evaluation of such tests' incremental value, defining outcomes that reflect each test's purpose (for example, transmissions averted) and comparing systems with the test against those without, in terms of those outcomes. Incremental value can also be measured in units of outcome per incremental unit of resource (for example, money or human capacity). Using a novel, simplified model of tuberculosis transmission that addresses some of the limitations of earlier tuberculosis diagnostic models, we demonstrate that the incremental value of any novel test depends not just on its accuracy, but also on elements such as patient behaviour, tuberculosis natural history and health systems. By integrating these factors into a single unified framework, we advance an approach to the evaluation of new diagnostic tests for tuberculosis that considers the incremental value at the population level and demonstrates how additional data could inform more-effective implementation of tuberculosis diagnostic tests under various conditions

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Section: Box 1 | Estimating the Incremental Value Of Tuberculosis Diamentioning

confidence: 85%

Understanding the incremental value of novel diagnostic tests for tuberculosis

Arinaminpathy

Dowdy

2015

Nature

109

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“…Recurrent efforts at active case finding may prove cheaper on a per-person basis; future studies should estimate the costs and cost-effectiveness of such efforts more precisely. Importantly, although we calibrated our model to a global-average incidence, concentrating efforts on those at highest risk (including people previously treated for TB [15] and residents of geographic "hotspots" [41]) could improve efficiency substantially. In areas characterized by prolonged patient delay (i.e., long prediagnostic period), "enhanced" strategies aiming to reduce that delay are also important considerations ( Figures 3E and 3F), but these strategies should not be universally assumed to have substantial population-level impact.…”

Section: Discussionmentioning

confidence: 99%

Is Passive Diagnosis Enough?

Dowdy

Basu

Andrews

2013

Am J Respir Crit Care Med

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Rationale: Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited. Objectives: To estimate the population-level impact of TB casefinding strategies in the presence of subclinical and prediagnostic disease. Methods: We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active"). Measurements and Main Results: If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase. Conclusions: Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection.Keywords: tuberculosis; diagnostic techniques and procedures; models; theoretical; epidemiology Improved diagnosis is a cornerstone of current efforts to control tuberculosis (TB) (1). For the last 15 years, the World Health Organization (WHO) and Stop TB Partnership have focused on improving TB case detection and treatment success, in part because key mathematical models predicted that meeting these targets would result in improved disease control (2). Although the directly observed therapy, short-course strategy has been scaled up globally and has saved more than 1 million lives (3), 1.4 million people still die every year from TB (4). Most of these deaths reflect diagnosis that is either delayed, missed, or never attempted. Strategies for improving TB diagnosis generally take one of three forms: (1) improvement of the "passive" diagnostic system (e.g., deploying new diagnostic tools, such as Xpert MTB/RIF [5,6] for diagnosis of people who present with TB symptoms); (2) "enhanced" diagnosis that aims to reduce delays in diagnosis for patients with recognizable symptoms, such as community awareness campaigns (7) and improved access to TB diagnostic services (8); and (3) "active" strategies that do not rely on patient presentation (e.g., household surveys [9], contact in...

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“…110 Geospatial and molecular epidemiology could allow us to capitalise on existing epidemiological, demographic, health service resource usage data. 111 Combined TB and HIV interventions are essential if any gains made through TB screening are to be maintained in high HIV prevalence settings, and they require joint planning, implementation and financing from the early stages of planning. Effective linkage to treatment and prevention of both TB and HIV needs to be the focus of special attention for both TB and HIV screening.…”

Section: Discussionmentioning

confidence: 99%

Tuberculosis screening in high human immunodeficiency virus prevalence settings: turning promise into reality [State of the art series. Active case finding/screening. Number 5 in the series]

Corbett

MacPherson²

2013

int j tuberc lung dis

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SUMMARYTwenty years of sky-high tuberculosis (TB) incidence rates and high TB mortality in high human immunodeficiency virus (HIV) prevalence countries have so far not been matched by the same magnitude or breadth of responses as seen in malaria or HIV programmes. Instead, recommendations have been narrowly focused on people presenting to health facilities for investigation of TB symptoms, or for HIV testing and care. However, despite the recent major investment and scale-up of TB and HIV services, undiagnosed TB remains highly prevalent at community level, implying that diagnosis of TB remains slow and incomplete. This maintains high transmission rates and exposes people living with HIV to high rates of morbidity and mortality.More intensive use of TB screening, with broader definitions of target populations, expanded indications for screening both inside and outside of health facilities, and appropriate selection of new diagnostic tools, offers the prospect of rapidly improving population-level control of TB. Diagnostic accuracy of suitable (high throughput) algorithms remains the major barrier to realising this goal.In the present study, we review the evidence available to guide expanded TB screening in HIVprevalent settings, ideally through combined TB-HIV interventions that provide screening for both TB and HIV, and maximise entry to HIV and TB care and prevention. Ideally, we would systematically test, treat and prevent TB and HIV comprehensively, offering both TB and HIV screening to all health facility attendees, TB households and all adults in the highest risk communities. However, we are still held back by inadequate diagnostics, financing and paucity of population-impact data. Relevant contemporary research showing the high need for potential gains, and pitfalls from expanded and intensified TB screening in high HIV prevalence settings are discussed in this review. In high human immunodeficiency virus (HIV) prevalence settings, population-level tuberculosis (TB) incidence increased in parallel with adult HIV prevalence in the 1990s and remains extremely high, with over 1% of adults diagnosed with TB each year in many Southern African towns. 1 Outbreaks of multi-and extensively drug-resistant TB (XDR-TB) have been generated in HIV care clinics, and then spread into general communities. 2,3 Autopsy studies show that TB is the single biggest killer of people living with HIV (PLHIV), being the cause in 32% to 45% of HIV-related deaths 4 and with a high proportion of fatal cases undiagnosed in life. 4,5 Of the estimated 430 000 TB-related deaths among PLHIV during 2011, 79% were in Africa. These stark facts demonstrate the urgent need to strengthen TB prevention and care services using all available approaches, including more ambitious TB screening strategies.TB screening is the first step in both anti-tuberculosis treatment and TB prevention pathways, and has an integral place in routine HIV care and infection control. Key potential entry points for TB screening are illustrated in Figure 1. TB screening c...

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Heterogeneity in tuberculosis transmission and the role of geographic hotspots in propagating epidemics

Cited by 131 publications

References 26 publications

Understanding the incremental value of novel diagnostic tests for tuberculosis

Understanding the incremental value of novel diagnostic tests for tuberculosis

Is Passive Diagnosis Enough?

Tuberculosis screening in high human immunodeficiency virus prevalence settings: turning promise into reality [State of the art series. Active case finding/screening. Number 5 in the series]

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