Ending tuberculosis in a post-COVID-19 world: a person-centred, equity-oriented approach.

The COVID-19 pandemic has disrupted systems of care for infectious diseases-including tuberculosis-and has exposed pervasive inequities that have long marred efforts to combat these diseases. The resulting health disparities often intersect at the individual and community levels in ways that heighten vulnerability to tuberculosis. Effective responses to tuberculosis (and other infectious diseases) must respond to these realities. Unfortunately, current tuberculosis programmes are generally not designed from the perspectives of affected individuals and fail to address structural determinants of health disparities. We describe a person-centred, equity-oriented response that would identify and focus on communities affected by disparities, tailor interventions to the mechanisms by which disparities worsen tuberculosis, and address upstream determinants of those disparities. We detail four key elements of the approach (data collection, programme design, implementation, and sustainability). We then illustrate how organisations at multiple levels might partner and adapt current practices to incorporate these elements. Such an approach could generate more substantial, sustainable, and equitable reductions in tuberculosis burden at the community level, highlighting the urgency of restructuring post-COVID-19 health systems in a more person-centred, equity-oriented way.

Symptom-based vs asymptomatic testing for controlling SARS-CoV-2 transmission in low- and middle-income countries: A modelling analysis.

BACKGROUND: Diagnostic testing plays a critical role in the global COVID-19 response. Polymerase chain reaction (PCR) tests are highly accurate, but in resource-limited settings, limited capacity has led to testing delays; whereas lateral flow assays (LFAs) offer opportunities for rapid and affordable testing. We examined the potential epidemiological impact of different strategies for LFA deployment. METHODS: We developed a deterministic compartmental model of SARS-CoV-2 transmission, parameterised to resemble a large Indian city. We assumed that PCR would be used to test symptomatic individuals presenting to outpatient settings for care. We examined how the second epidemic wave in India could have been mitigated by LFA deployment in its early stages by comparing two strategies: (i) community-based screening, using LFAs to test a proportion of the population, irrespective of symptoms (in addition to symptom-driven PCR), and (ii) symptom-driven outpatient testing, using LFAs to replace PCR. RESULTS: Model projections suggest that a stock of 25 million LFAs, used over a 600-day period in a city of 20 million people, would reduce the cumulative symptomatic incidence of COVID-19 by 0.44% if used for community-based screening, and by 13% if used to test symptomatic outpatients, relative to a no-LFA, PCR-only scenario. Sensitivity analysis suggests that outpatient testing would be more efficient in reducing transmission than community-based screening, when at least 5% of people with symptomatic COVID-19 seek care, and at least 10% of SARS-CoV-2 infections develop symptoms. Under both strategies, however, 2% of the population would be unnecessarily isolated. INTERPRETATION: In this emblematic setting, LFAs would reduce transmission most efficiently when used to test symptomatic individuals in outpatient settings. To avoid large numbers of unnecessary isolations, mass testing with LFAs should be considered as a screening tool, with follow-up confirmation. Future work should address strategies for targeted community-based LFA testing, such as contact tracing.

A Systematic Review of the Costs Relating to Non-pharmaceutical Interventions Against Infectious Disease Outbreaks.

BACKGROUND: Non-pharmaceutical interventions (NPIs) are the cornerstone of infectious disease outbreak response in the absence of effective pharmaceutical interventions. Outbreak strategies often involve combinations of NPIs that may change according to disease prevalence and population response. Little is known with regard to how costly each NPI is to implement. This information is essential to inform policy decisions for outbreak response. OBJECTIVE: To address this gap in existing literature, we conducted a systematic review on outbreak costings and simulation studies related to a number of NPI strategies, including isolating infected individuals, contact tracing and quarantine, and school closures. METHODS: Our search covered the MEDLINE and EMBASE databases, studies published between 1990 and 24 March 2020 were included. We included studies containing cost data for our NPIs of interest in pandemic, epidemic, and outbreak response scenarios. RESULTS: We identified 61 relevant studies. There was substantial heterogeneity in the cost components recorded for NPIs in outbreak costing studies. The direct costs of NPIs for which costing studies existed also ranged widely: isolating infected individuals per case: US$141.18 to US$1042.68 (2020 values), tracing and quarantine of contacts per contact: US$40.73 to US$93.59, social distancing: US$33.76 to US$167.92, personal protection and hygiene: US$0.15 to US$895.60. CONCLUSION: While there are gaps and heterogeneity in available cost data, the findings of this review and the collated cost database serve as an important resource for evidence-based decision-making for estimating costs pertaining to NPI implementation in future outbreak response policies.

Trade-offs between cost and accuracy in active case finding for tuberculosis: A dynamic modelling analysis.

BACKGROUND: Active case finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of TB cases, yet is cheap and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF in ACF in a high-burden setting? METHODS AND FINDINGS: We constructed a dynamic transmission model of TB, calibrated to be consistent with an urban slum population in India. We applied this model to compare the potential cost and impact of 2 hypothetical approaches following initial symptom screening: (i) 'moderate accuracy' testing employing a microscopy-like test (i.e., lower cost but also lower accuracy) for bacteriological confirmation and (ii) 'high accuracy' testing employing an Xpert-like test (higher cost but also higher accuracy, while also detecting rifampicin resistance). Results suggest that ACF using a moderate-accuracy test could in fact cost more overall than using a high-accuracy test. Under an illustrative budget of US$20 million in a slum population of 2 million, high-accuracy testing would avert 1.14 (95% credible interval 0.75-1.99, with p = 0.28) cases relative to each case averted by moderate-accuracy testing. Test specificity is a key driver: High-accuracy testing would be significantly more impactful at the 5% significance level, as long as the high-accuracy test has specificity at least 3 percentage points greater than the moderate-accuracy test. Additional factors promoting the impact of high-accuracy testing are that (i) its ability to detect rifampicin resistance can lead to long-term cost savings in second-line treatment and (ii) its higher sensitivity contributes to the overall cases averted by ACF. Amongst the limitations of this study, our cost model has a narrow focus on the commodity costs of testing and treatment; our estimates should not be taken as indicative of the overall cost of ACF. There remains uncertainty about the true specificity of tests such as smear and Xpert-like tests in ACF, relating to the accuracy of the reference standard under such conditions. CONCLUSIONS: Our results suggest that cheaper diagnostics do not necessarily translate to less costly ACF, as any savings from the test cost can be strongly outweighed by factors including false-positive TB treatment, reduced sensitivity, and foregone savings in second-line treatment. In resource-limited settings, it is therefore important to take all of these factors into account when designing cost-effective strategies for ACF.

The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.

BACKGROUND: Routine services for tuberculosis (TB) are being disrupted by stringent lockdowns against the novel SARS-CoV-2 virus. We sought to estimate the potential long-term epidemiological impact of such disruptions on TB burden in high-burden countries, and how this negative impact could be mitigated. METHODS: We adapted mathematical models of TB transmission in three high-burden countries (India, Kenya and Ukraine) to incorporate lockdown-associated disruptions in the TB care cascade. The anticipated level of disruption reflected consensus from a rapid expert consultation. We modelled the impact of these disruptions on TB incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. FINDINGS: Even temporary disruptions can cause long-term increases in TB incidence and mortality. If lockdown-related disruptions cause a temporary 50% reduction in TB transmission, we estimated that a 3-month suspension of TB services, followed by 10 months to restore to normal, would cause, over the next 5 years, an additional 1⋅19 million TB cases (Crl 1⋅06-1⋅33) and 361,000 TB deaths (CrI 333-394 thousand) in India, 24,700 (16,100-44,700) TB cases and 12,500 deaths (8.8-17.8 thousand) in Kenya, and 4,350 (826-6,540) cases and 1,340 deaths (815-1,980) in Ukraine. The principal driver of these adverse impacts is the accumulation of undetected TB during a lockdown. We demonstrate how long term increases in TB burden could be averted in the short term through supplementary "catch-up" TB case detection and treatment, once restrictions are eased. INTERPRETATION: Lockdown-related disruptions can cause long-lasting increases in TB burden, but these negative effects can be mitigated with rapid restoration of TB services, and targeted interventions that are implemented as soon as restrictions are lifted. FUNDING: USAID and Stop TB Partnership.