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1.
Nat Commun ; 12(1): 424, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462224

RESUMEN

There have been notable advances in the development of vaccines against active tuberculosis (TB) disease for adults and adolescents. Using mathematical models, we seek to estimate the potential impact of a post-exposure TB vaccine, having 50% efficacy in reducing active disease, on global rifampicin-resistant (RR-) TB burden. In 30 countries that together accounted for 90% of global RR-TB incidence in 2018, a future TB vaccine could avert 10% (95% credible interval: 9.7-11%) of RR-TB cases and 7.3% (6.6-8.1%) of deaths over 2020-2035, with India, China, Indonesia, Pakistan, and the Russian Federation having the greatest contribution. This impact would increase to 14% (12-16%) and 31% (29-33%) respectively, when combined with improvements in RR-TB diagnosis and treatment relative to a scenario of no vaccine and no such improvements. A future TB vaccine could have important implications for the global control of RR-TB, especially if implemented alongside enhancements in management of drug resistance.


Asunto(s)
Antituberculosos/farmacología , Carga Global de Enfermedades , Profilaxis Posexposición/métodos , Vacunas contra la Tuberculosis/administración & dosificación , Tuberculosis/epidemiología , Adolescente , Adulto , Antituberculosos/uso terapéutico , Simulación por Computador , Farmacorresistencia Bacteriana/inmunología , Humanos , Incidencia , Modelos Estadísticos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Tuberculosis/prevención & control
2.
Sci Rep ; 11(1): 1835, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33469083

RESUMEN

India's lockdown and subsequent restrictions against SARS-CoV-2, if lifted without any other mitigations in place, could risk a second wave of infection. A test-and-isolate strategy, using PCR diagnostic tests, could help to minimise the impact of this second wave. Meanwhile, population-level serological surveillance can provide valuable insights into the level of immunity in the population. Using a mathematical model, consistent with an Indian megacity, we examined how seroprevalence data could guide a test-and-isolate strategy, for fully lifting restrictions. For example, if seroprevalence is 20% of the population, we show that a testing strategy needs to identify symptomatic cases within 5-8 days of symptom onset, in order to prevent a resurgent wave from overwhelming hospital capacity in the city. This estimate is robust to uncertainty in the effectiveness of the lockdown, as well as in immune protection against reinfection. To set these results in their economic context, we estimate that the weekly cost of such a PCR-based testing programme would be less than 2.1% of the weekly economic loss due to the lockdown. Our results illustrate how PCR-based testing and serological surveillance can be combined to design evidence-based policies, for lifting lockdowns in Indian cities and elsewhere.


Asunto(s)
/prevención & control , Modelos Teóricos , /epidemiología , /virología , Humanos , India/epidemiología , Vigilancia de la Población , Prevalencia , Cuarentena/economía , /aislamiento & purificación
3.
PLoS Med ; 17(12): e1003456, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33264288

RESUMEN

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.

4.
PLoS Med ; 17(12): e1003466, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33306694

RESUMEN

BACKGROUND: Lateral flow urine lipoarabinomannan (LAM) tests could offer important new opportunities for the early detection of tuberculosis (TB). The currently licensed LAM test, Alere Determine TB LAM Ag ('LF-LAM'), performs best in the sickest people living with HIV (PLHIV). However, the technology continues to improve, with newer LAM tests, such as Fujifilm SILVAMP TB LAM ('SILVAMP-LAM') showing improved sensitivity, including amongst HIV-negative patients. It is important to anticipate the epidemiological impact that current and future LAM tests may have on TB incidence and mortality. METHODS AND FINDINGS: Concentrating on South Africa, we examined the impact that widening LAM test eligibility would have on TB incidence and mortality. We developed a mathematical model of TB transmission to project the impact of LAM tests, distinguishing 'current' tests (with sensitivity consistent with LF-LAM), from hypothetical 'future' tests (having sensitivity consistent with SILVAMP-LAM). We modelled the impact of both tests, assuming full adoption of the 2019 WHO guidelines for the use of these tests amongst those receiving HIV care. We also simulated the hypothetical deployment of future LAM tests for all people presenting to care with TB symptoms, not restricted to PLHIV. Our model projects that 2,700,000 (95% credible interval [CrI] 2,000,000-3,600,000) and 420,000 (95% CrI 350,000-520,000) cumulative TB incident cases and deaths, respectively, would occur between 2020 and 2035 if the status quo is maintained. Relative to this comparator, current and future LAM tests would respectively avert 54 (95% CrI 33-86) and 90 (95% CrI 55-145) TB deaths amongst inpatients between 2020 and 2035, i.e., reductions of 5% (95% CrI 4%-6%) and 9% (95% CrI 7%-11%) in inpatient TB mortality. This impact in absolute deaths averted doubles if testing is expanded to include outpatients, yet remains <1% of country-level TB deaths. Similar patterns apply to incidence results. However, deploying a future LAM test for all people presenting to care with TB symptoms would avert 470,000 (95% CrI 220,000-870,000) incident TB cases (18% reduction, 95% CrI 9%-29%) and 120,000 (95% CrI 69,000-210,000) deaths (30% reduction, 95% CrI 18%-44%) between 2020 and 2035. Notably, this increase in impact arises largely from diagnosis of TB amongst those with HIV who are not yet in HIV care, and who would thus be ineligible for a LAM test under current guidelines. Qualitatively similar results apply under an alternative comparator assuming expanded use of GeneXpert MTB/RIF ('Xpert') for TB diagnosis. Sensitivity analysis demonstrates qualitatively similar results in a setting like Kenya, which also has a generalised HIV epidemic, but a lower burden of HIV/TB coinfection. Amongst limitations of this analysis, we do not address the cost or cost-effectiveness of future tests. Our model neglects drug resistance and focuses on the country-level epidemic, thus ignoring subnational variations in HIV and TB burden. CONCLUSIONS: These results suggest that LAM tests could have an important effect in averting TB deaths amongst PLHIV with advanced disease. However, achieving population-level impact on the TB epidemic, even in high-HIV-burden settings, will require future LAM tests to have sufficient performance to be deployed more broadly than in HIV care.

5.
EClinicalMedicine ; 28: 100603, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33134905

RESUMEN

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.

6.
medRxiv ; 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32995809

RESUMEN

The novel SARS-CoV-2 virus shows marked heterogeneity in its transmission. Here, we used data collected from contact tracing during the lockdown in Punjab, a major state in India, to quantify this heterogeneity, and to examine implications for transmission dynamics. We found evidence of heterogeneity acting at multiple levels: in the number of potentially infectious contacts per index case, and in the per-contact risk of infection. Incorporating these findings in simple mathematical models of disease transmission reveals that these heterogeneities act in combination to strongly influence transmission dynamics. Standard approaches, such as representing heterogeneity through secondary case distributions, could be biased by neglecting these underlying interactions between heterogeneities. We discuss implications for policy, and for more efficient contact tracing in resource-constrained settings such as India. Our results highlight how contact tracing, an important public health measure, can also provide important insights into epidemic spread and control.

7.
BMC Med ; 18(1): 163, 2020 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-32684164

RESUMEN

BACKGROUND: The prevention of tuberculosis (TB) is key for accelerating current, slow declines in TB burden. The 2018 World Health Organization (WHO) guidelines on eligibility for preventive therapy to treat latent TB infection (LTBI) include people living with human immunodeficiency virus (PLHIV), household contacts of TB patients including children, and those with clinical conditions including silicosis, dialysis, transplantation, etc. and other country-specific groups. We aimed to estimate the potential impact of full implementation of these guidelines in the WHO South-East Asian (SEA) Region, which bears the largest burden of TB and LTBI amongst the WHO regions. METHODS: We developed mathematical models of TB transmission dynamics, calibrated individually to each of the 11 countries in the region. We modelled preventive therapy in the absence of other TB interventions. As an alternative comparator, reflecting ongoing developments in TB control in the region, we also simulated improvements in the treatment cascade for active TB, including private sector engagement and intensified case-finding. Relative to both scenarios, for each country in the region, we projected TB cases and deaths averted between 2020 and 2030, by full uptake of preventive therapy, defined as comprehensive coverage amongst eligible populations as per WHO guidelines, and assuming outcomes consistent with clinical trials. We also performed sensitivity analysis to illustrate impact under less-than-optimal conditions. RESULTS: At the regional level, full uptake of preventive therapy amongst identified risk groups would reduce annual incidence rates in 2030 by 8.30% (95% CrI 6.48-10.83) relative to 2015, in the absence of any additional interventions. If implemented against a backdrop of improved TB treatment cascades, preventive therapy would achieve an incremental 6.93 percentage points (95% CrI 5.81-8.51) of reduction in annual incidence rates, compared to 2015. At the regional level, the numbers of individuals with latent TB infection that need to be treated to avert 1 TB case is 64 (95% CrI 55-74). Sensitivity analysis illustrates that results for impact are roughly proportional to 'effective coverage' (the product of actual coverage and effectiveness of the regimen). CONCLUSIONS: Full implementation of WHO guidelines is important for ending TB in the SEA Region. Although future strategies will need to be expanded to the population level, to achieve large declines in TB incidence, the uptake of current tools can offer a valuable step in this direction.

8.
J R Soc Interface ; 17(167): 20200075, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32486949

RESUMEN

The largest ever Sri Lankan dengue outbreak of 2017 provides an opportunity for investigating the relative contributions of climatological, epidemiological and sociological drivers on the epidemic patterns of this clinically important vector-borne disease. To do so, we develop a climatologically driven disease transmission framework for dengue virus using spatially resolved temperature and precipitation data as well as the time-series susceptible-infected-recovered (SIR) model. From this framework, we first demonstrate that the distinct climatological patterns encountered across the island play an important role in establishing the typical yearly temporal dynamics of dengue, but alone are unable to account for the epidemic case numbers observed in Sri Lanka during 2017. Using a simplified two-strain SIR model, we demonstrate that the re-introduction of a dengue virus serotype that had been largely absent from the island in previous years may have played an important role in driving the epidemic, and provide a discussion of the possible roles for extreme weather events and human mobility patterns on the outbreak dynamics. Lastly, we provide estimates for the future burden of dengue across Sri Lanka using the Coupled Model Intercomparison Phase 5 climate projections. Critically, we demonstrate that climatological and serological factors can act synergistically to yield greater projected case numbers than would be expected from the presence of a single driver alone. Altogether, this work provides a holistic framework for teasing apart and analysing the various complex drivers of vector-borne disease outbreak dynamics.

9.
PLoS Comput Biol ; 16(6): e1007892, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32584807

RESUMEN

Seasonal influenza A viruses of humans evolve rapidly due to strong selection pressures from host immune responses, principally on the hemagglutinin (HA) viral surface protein. Based on mouse transmission experiments, a proposed mechanism for immune evasion consists of increased avidity to host cellular receptors, mediated by electrostatic charge interactions with negatively charged cell surfaces. In support of this, the HA charge of the globally circulating H3N2 has increased over time since its pandemic. However, the same trend was not seen in H1N1 HA sequences. This is counter-intuitive, since immune escape due to increased avidity (due itself to an increase in charge) was determined experimentally. Here, we explore whether patterns of local charge of H1N1 HA can explain this discrepancy and thus further associate electrostatic charge with immune escape and viral evolutionary dynamics. Measures of site-wise functional selection and expected charge computed from deep mutational scan data on an early H1N1 HA yield a striking division of residues into three groups, separated by charge. We then explored evolutionary dynamics of these groups from 1918 to 2008. In particular, one group increases in net charge over time and consists of sites that are evolving the fastest, that are closest to the receptor binding site (RBS), and that are exposed to solvent (i.e., on the surface). By contrast, another group decreases in net charge and consists of sites that are further away from the RBS and evolving slower, but also exposed to solvent. The last group consists of those sites in the HA core, with no change in net charge and that evolve very slowly. Thus, there is a group of residues that follows the same trend as seen for the entire H3N2 HA. It is possible that the H1N1 HA is under other biophysical constraints that result in compensatory decreases in charge elsewhere on the protein. Our results implicate localized charge in HA interactions with host cells, and highlight how deep mutational scan data can inform evolutionary hypotheses.


Asunto(s)
Evolución Molecular , Subtipo H1N1 del Virus de la Influenza A/genética , Mutación , Humanos , Estaciones del Año
10.
PLoS Med ; 17(5): e1003039, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32407407

RESUMEN

BACKGROUND: Tuberculosis (TB) incidence in India continues to be high due, in large part, to long delays experienced by patients before successful diagnosis and treatment initiation, especially in the private sector. This diagnostic delay is driven by patients' inclination to switch between different types of providers and providers' inclination to delay ordering of accurate diagnostic tests relevant to TB. Our objective is to quantify the impact of changes in these behavioral characteristics of providers and patients on diagnostic delay experienced by pulmonary TB patients. METHODS AND FINDINGS: We developed a discrete event simulation model of patients' diagnostic pathways that captures key behavioral characteristics of providers (time to order a test) and patients (time to switch to another provider). We used an expectation-maximization algorithm to estimate the parameters underlying these behavioral characteristics, with quantitative data encoded from detailed interviews of 76 and 64 pulmonary TB patients in the 2 Indian cities of Mumbai and Patna, respectively, which were conducted between April and August 2014. We employed the estimated model to simulate different counterfactual scenarios of diagnostic pathways under altered behavioral characteristics of providers and patients to predict their potential impact on the diagnostic delay. Private healthcare providers including chemists were the first point of contact for the majority of TB patients in Mumbai (70%) and Patna (94%). In Mumbai, 45% of TB patients first approached less-than-fully-qualified providers (LTFQs), who take 28.71 days on average for diagnosis. About 61% of these patients switched to other providers without a diagnosis. Our model estimates that immediate testing for TB by LTFQs at the first visit (at the current level of diagnostic accuracy) could reduce the average diagnostic delay from 35.53 days (95% CI: 34.60, 36.46) to 18.72 days (95% CI: 18.01, 19.43). In Patna, 61% of TB patients first approached fully qualified providers (FQs), who take 9.74 days on average for diagnosis. Similarly, immediate testing by FQs at the first visit (at the current level of diagnostic accuracy) could reduce the average diagnostic delay from 23.39 days (95% CI: 22.77, 24.02) to 11.16 days (95% CI: 10.52, 11.81). Improving the diagnostic accuracy of providers per se, without reducing the time to testing, was not predicted to lead to any reduction in diagnostic delay. Our study was limited because of its restricted geographic scope, small sample size, and possible recall bias, which are typically associated with studies of patient pathways using patient interviews. CONCLUSIONS: In this study, we found that encouraging private providers to order definitive TB diagnostic tests earlier during patient consultation may have substantial impact on reducing diagnostic delay in these urban Indian settings. These results should be combined with disease transmission models to predict the impact of changes in provider behavior on TB incidence.


Asunto(s)
Diagnóstico Tardío/prevención & control , Modelos Teóricos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico , Antituberculosos/uso terapéutico , Conducta/fisiología , Estudios Transversales , Personal de Salud , Humanos , India , Sector Privado , Tuberculosis/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología
11.
Indian J Med Res ; 151(2 & 3): 190-199, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32362645

RESUMEN

Background & objectives: Coronavirus disease 2019 (COVID-19) has raised urgent questions about containment and mitigation, particularly in countries where the virus has not yet established human-to-human transmission. The objectives of this study were to find out if it was possible to prevent, or delay, the local outbreaks of COVID-19 through restrictions on travel from abroad and if the virus has already established in-country transmission, to what extent would its impact be mitigated through quarantine of symptomatic patients? Methods: These questions were addressed in the context of India, using simple mathematical models of infectious disease transmission. While there remained important uncertainties in the natural history of COVID-19, using hypothetical epidemic curves, some key findings were illustrated that appeared insensitive to model assumptions, as well as highlighting critical data gaps. Results: It was assumed that symptomatic quarantine would identify and quarantine 50 per cent of symptomatic individuals within three days of developing symptoms. In an optimistic scenario of the basic reproduction number (R0) being 1.5, and asymptomatic infections lacking any infectiousness, such measures would reduce the cumulative incidence by 62 per cent. In the pessimistic scenario of R0=4, and asymptomatic infections being half as infectious as symptomatic, this projected impact falls to two per cent. Interpretation & conclusions: Port-of-entry-based entry screening of travellers with suggestive clinical features and from COVID-19-affected countries, would achieve modest delays in the introduction of the virus into the community. Acting alone, however, such measures would be insufficient to delay the outbreak by weeks or longer. Once the virus establishes transmission within the community, quarantine of symptomatics may have a meaningful impact on disease burden. Model projections are subject to substantial uncertainty and can be further refined as more is understood about the natural history of infection of this novel virus. As a public health measure, health system and community preparedness would be critical to control any impending spread of COVID-19 in the country.


Asunto(s)
Control de Enfermedades Transmisibles/métodos , Infecciones por Coronavirus/prevención & control , Modelos Teóricos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Número Básico de Reproducción , Betacoronavirus , Infecciones por Coronavirus/epidemiología , Monitoreo Epidemiológico , Humanos , Incidencia , India , Tamizaje Masivo , Neumonía Viral/epidemiología , Salud Pública , Cuarentena
12.
Nature ; 581(7806): 94-99, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32376956

RESUMEN

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.


Asunto(s)
Antibacterianos , Países en Desarrollo/economía , Utilización de Medicamentos/estadística & datos numéricos , Vacunas , Antibacterianos/administración & dosificación , Antibacterianos/economía , Preescolar , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Diarrea/virología , Farmacorresistencia Microbiana , Utilización de Medicamentos/economía , Humanos , Incidencia , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Vacunas/administración & dosificación , Vacunas/economía , Vacunas/inmunología , Organización Mundial de la Salud/organización & administración
13.
BMJ Glob Health ; 5(3): e002073, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32201625

RESUMEN

The Southeast Asia Region continues to battle tuberculosis (TB) as one of its most severe health and development challenges. Unless there is a substantial increase in investments for TB prevention, diagnosis, care and treatment, there will be catastrophic effects for the region. The uncontrolled TB burden impacts socioeconomic development and increase of drug resistance in the region. Based on epidemiological inputs from a mathematical model, a costing analysis estimates that the desired targets of ending TB are achievable with additional interventions, and critical thresholds require an increase in spending by almost double the current levels. The data source for financial allocation to TB programmes is the report submitted by countries to WHO, while projections are based on modelling. The model accounts for funding needs for all strategies based on published data and accounts for programme and patient costs. This paper delineates the resource needs, availability and gaps of ending TB in the region. It is estimated that close to US$2 billion per year are needed in the region for TB-related activities for a meaningful bending of the incidence curve towards ending TB.

14.
PLoS One ; 15(3): e0230808, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32218585

RESUMEN

There is increasing interest in future, highly-potent 'pan-TB' regimens against tuberculosis (TB), that may be equally effective in both drug-susceptible and rifampicin-resistant (RR) forms of TB. Taking the example of India, the country with the world's largest burden of TB, we show that adoption of these regimens could be: (i) epidemiologically impactful, and (ii) cost-saving to the national TB programme, even if the regimen itself is more costly than current TB treatment. Mathematical modelling suggests that deployment of a pan-TB regimen in 2022 would reduce the annual incidence of TB in 2030 by 23.9% [95% Bayesian credible intervals [CrI] 17.6-30.8%] if used to treat all TB cases, and by 2.30% [95% CrI 1.57-3.48%] if used to treat only RR-TB. Notably, with a regimen costing less than USD 359 (95% CrI 287-441), treating all diagnosed TB cases with the pan-TB regimen yielded greater cost-savings than treating just those diagnosed with RR-TB. One limitation of our approach is that it does not capture the risk of resistance to the new regimen. We discuss ways in which this risk could be mitigated using modern adherence support mechanisms, as well as drug sensitivity testing at the point of TB diagnosis, to prevent new resistant forms from becoming established. A combination of such approaches would be important for maximising the useful lifetime of any future regimen.


Asunto(s)
Antituberculosos/uso terapéutico , Descubrimiento de Drogas , Modelos Estadísticos , Tuberculosis/tratamiento farmacológico , Humanos , India , Rifampin/uso terapéutico
15.
BMC Infect Dis ; 20(1): 191, 2020 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-32131756

RESUMEN

BACKGROUND: Tuberculosis (TB) burden shows wide disparities across ages in Taiwan. In 2016, the age-specific notification rate in those older than 65 years old was about 100 times as much as in those younger than 15 years old (185.0 vs 1.6 per 100,000 population). Similar patterns are observed in other intermediate TB burden settings. However, driving mechanisms for such age disparities are not clear and may have importance for TB control efforts. METHODS: We hypothesised three mechanisms for the age disparity in TB burden: (i) older age groups bear a higher risk of TB progression due to immune senescence, (ii) elderly cases acquired TB infection during a past period of high transmission, which has since rapidly declined and thus contributes to little recent infections, and (iii) assortative mixing by age allows elders to maintain a higher risk of TB infection, while limiting spillover transmission to younger age groups. We developed a series of dynamic compartmental models to incorporate these mechanisms, individually and in combination. The models were calibrated to the TB notification rates in Taiwan over 1997-2016 and evaluated by goodness-of-fit to the age disparities and the temporal trend in the TB burden, as well as the deviance information criterion (DIC). According to the model performance, we compared contributions of the hypothesised mechanisms. RESULTS: The 'full' model including all the three hypothesised mechanisms best captured the age disparities and temporal trend of the TB notification rates. However, dropping individual mechanisms from the full model in turn, we found that excluding the mechanism of assortative mixing yielded the least change in goodness-of-fit. In terms of their influence on the TB dynamics, the major contribution of the 'immune senescence' and 'assortative mixing' mechanisms was to create disparate burden among age groups, while the 'declining transmission' mechanism served to capture the temporal trend of notification rates. CONCLUSIONS: In settings such as Taiwan, the current TB burden in the elderly may be impacted more by prevention of active disease following latent infection, than by case-finding for blocking transmission. Further studies on these mechanisms are needed to disentangle their impacts on the TB epidemic and develop corresponding control strategies.


Asunto(s)
Disparidades en el Estado de Salud , Tuberculosis Latente/epidemiología , Tuberculosis Latente/transmisión , Adolescente , Adulto , Factores de Edad , Anciano , Envejecimiento/inmunología , Humanos , Incidencia , Tuberculosis Latente/mortalidad , Masculino , Persona de Mediana Edad , Modelos Teóricos , Taiwán/epidemiología , Adulto Joven
16.
J Infect Dis ; 220(220 Suppl 3): S116-S125, 2019 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-31593600

RESUMEN

Approximately 3.6 million cases of active tuberculosis (TB) go potentially undiagnosed annually, partly due to limited access to confirmatory diagnostic tests, such as molecular assays or mycobacterial culture, in community and primary healthcare settings. This article provides guidance for TB triage test evaluations. A TB triage test is designed for use in people with TB symptoms and/or significant risk factors for TB. Triage tests are simple and low-cost tests aiming to improve ease of access and implementation (compared with confirmatory tests) and decrease the proportion of patients requiring more expensive confirmatory testing. Evaluation of triage tests should occur in settings of intended use, such as community and primary healthcare centers. Important considerations for triage test evaluation include study design, population, sample type, test throughput, use of thresholds, reference standard (ideally culture), and specimen flow. The impact of a triage test will depend heavily on issues beyond accuracy, primarily centered on implementation.


Asunto(s)
Bioensayo/normas , Pruebas Diagnósticas de Rutina/normas , Mycobacterium tuberculosis/aislamiento & purificación , Guías de Práctica Clínica como Asunto , Triaje/métodos , Tuberculosis Pulmonar/diagnóstico , Adulto , Bioensayo/economía , Biomarcadores/sangre , Biomarcadores/orina , Cultivo de Sangre/normas , Niño , Estudios de Cohortes , Estudios Transversales , Pruebas Diagnósticas de Rutina/economía , Humanos , Mycobacterium tuberculosis/patogenicidad , Mycobacterium tuberculosis/fisiología , Estándares de Referencia , Proyectos de Investigación , Factores de Riesgo , Sensibilidad y Especificidad , Esputo/microbiología , Triaje/economía , Triaje/normas , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/fisiopatología , Organización Mundial de la Salud
18.
Indian J Med Res ; 149(4): 517-527, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-31411176

RESUMEN

Background & objectives: To support recent political commitments to end tuberculosis (TB) in the World Health Organization South-East Asian Region (SEAR), there is a need to understand by what measures, and with what investment, these goals could be reached. These questions were addressed by using mathematical models of TB transmission by doing the analysis on a country-by-country basis in SEAR. Methods: A dynamical model of TB transmission was developed, in consultation with each of the 11 countries in the SEAR. Three intervention scenarios were examined: (i) strengthening basic TB services (including private sector engagement), (ii) accelerating TB case-finding and notification, and (iii) deployment of a prognostic biomarker test by 2025, to guide mass preventive therapy of latent TB infection. Each scenario was built on the preceding ones, in successive combination. Results: Comprehensive improvements in basic TB services by 2020, in combination with accelerated case-finding to increase TB detection by at least two-fold by 2020, could lead to a reduction in TB incidence rates in SEAR by 67.3 per cent [95% credible intervals (CrI) 65.3-69.8] and TB deaths by 80.9 per cent (95% CrI 77.9-84.7) in 2035, relative to 2015. These interventions alone would require an additional investment of at least US$ 25 billion. However, their combined effect is insufficient to reach the end TB targets of 80 per cent by 2030 and 90 per cent by 2035. Model projections show how additionally, deployment of a biomarker test by 2025 could end TB in the region by 2035. Targeting specific risk groups, such as slum dwellers, could mitigate the coverage needed in the general population, to end TB in the Region. Interpretation & conclusions: While the scale-up of currently available strategies may play an important role in averting TB cases and deaths in the Region, there will ultimately be a need for novel, mass preventive measures, to meet the end TB goals. Achieving these impacts will require a substantial escalation in funding for TB control in the Region.


Asunto(s)
Tuberculosis Latente/epidemiología , Modelos Teóricos , Tuberculosis/epidemiología , Humanos , India/epidemiología , Tuberculosis Latente/microbiología , Tuberculosis Latente/prevención & control , Tuberculosis/microbiología , Tuberculosis/prevención & control , Organización Mundial de la Salud
19.
BMC Infect Dis ; 19(1): 539, 2019 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-31217003

RESUMEN

BACKGROUND: There is a pressing need for systematic approaches for monitoring how much TB treatment is ongoing in the private sector in India: both to cast light on the true scale of the problem, and to help monitor the progress of interventions currently being planned to address this problem. METHODS: We used commercially available data on the sales of rifampicin-containing drugs in the private sector, adjusted for data coverage and indication of use. We examined temporal, statewise trends in volumes (patient-months) of TB treatment from 2013 to 2016. We additionally analysed the proportion of drugs that were sold in combination packaging (designed to simplify TB treatment), or as loose pills. RESULTS: Drug sales suggest a steady trend of TB treatment dispensed by the private sector, from 18.4 million patient-months (95% CI 17.3-20.5) in 2013 to 16.8 patient-months (95% CI 15.5-19.0) in 2016. Overall, seven of 29 states in India accounted for more than 70% of national-level TB treatment volumes, including Uttar Pradesh, Maharashtra and Bihar. The overwhelming majority of TB treatment was dispensed not as loose pills, but in combination packaging with other TB drugs, accounting for over 96% of private sector TB treatment in 2017. CONCLUSIONS: Our findings suggest consistent levels of TB treatment in the private sector over the past 4 years, while highlighting specific states that should be prioritized for intervention. Drug sales data can be helpful for monitoring a system as large, disorganised and opaque as India's private sector.


Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Sector de Atención de Salud/tendencias , Tuberculosis/tratamiento farmacológico , Sector de Atención de Salud/economía , Humanos , India , Rifampin/uso terapéutico
20.
Lancet ; 393(10178): 1331-1384, 2019 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-30904263
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