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<ns4:p>Tuberculosis kills more people worldwide than any other single infectious disease agent, a threat made more dire by the spread of drug-resistant strains of <ns4:italic>Mycobacterium tuberculosis (Mtb)</ns4:italic>. Development of new vaccines capable of preventing TB disease and new <ns4:italic>Mtb</ns4:italic> infection are an essential component of the strategy to combat the TB epidemic. Accordingly, the WHO considers the development of new TB vaccines a major public health priority. In October 2017, the WHO convened a consultation with global leaders in the TB vaccine development field to emphasize the WHO commitment to this effort and to facilitate creative approaches to the discovery and development of TB vaccine candidates. This review summarizes the presentations at this consultation, updated with scientific literature references, and includes discussions of the public health need for a TB vaccine; the status of efforts to develop vaccines to replace or potentiate BCG in infants and develop new TB vaccines for adolescents and adults; strategies being employed to diversify vaccine platforms; and new animal models being developed to facilitate TB vaccine development. A perspective on the status of these efforts from the major funders and organizational contributors also is included. This presentation highlights the extraordinary progress being made to develop new TB vaccines and provided a clear picture of the exciting development pathways that are being explored.</ns4:p>
Author: Lewis K Schrager
Posted: December 17, 2018, 1:52 pm
Background
Tuberculosis is the leading single-pathogen cause of death worldwide, and China has the third largest number of cases worldwide. New tools, such as new vaccines, are needed to meet WHO tuberculosis goals. Tuberculosis vaccine development strategies mostly target infants or adolescents, but given China’s ageing epidemic, vaccinating older people might be important. We modelled the potential impact of new tuberculosis vaccines in China targeting adolescents (15–19 years) or older adults (60–64 years) with varying vaccine characteristics to inform strategic vaccine development.
Methods
A Mycobacterium tuberculosis transmission model was calibrated to age-stratified demographic and epidemiological data from China. Varying scenarios of vaccine implementation (age targeting [adolescents or older adults] and coverage [30% or 70%]) and characteristics (efficacy [40%, 60%, or 80%], duration of protection [10 years or 20 years], and host infection status required for efficacy [pre-infection, post-infection in latency, post-infection in latency or recovered, or pre-infection and post-infection]) were assessed. Primary outcomes were tuberculosis incidence and mortality rate reduction in 2050 in each vaccine scenario compared with the baseline (no new vaccine) scenario and cumulative number needed to vaccinate (NNV) per case or death averted, 2025–50.
Findings
By 2050, results suggest that 74·5% (uncertainty interval [UI] 70·2–78·6) of incident tuberculosis cases in China would occur in people aged 65 years or older, and 75·1% (66·8–80·7) of all cases would be due to reactivation, rather than new infection. All vaccine profiles delivered to older adults had higher population-level impact (reduction of incidence and mortality rates) and lower NNV per case and per death averted than if delivered to adolescents. For an intermediate vaccine scenario of 60% efficacy, 10-year protection, and 70% coverage, the reduction of tuberculosis incidence rates with older adult vaccination was 1·9 times (UI 1·5–2·6) to 157·5 times (119·3–225·6) greater than with adolescent vaccination, and the NNV was 0·011 times (0·008–0·014) to 0·796 times (0·632–0·970) lower. Furthermore, with older adult vaccination, post-infection vaccines provided substantially greater mortality and incidence rate reductions than pre-infection vaccines.
Interpretation
Adolescent-targeted tuberculosis vaccines, the focus of many development plans, would have only a small impact in ageing, reactivation-driven epidemics such as those in China. Instead, an efficacious post-infection vaccine delivered to older adults will be crucial to maximise population-level impact in this setting and would provide an important contribution towards achieving WHO goals. Older adults should be included in tuberculosis vaccine clinical development and implementation planning.
Author: Rebecca Harris
Posted: December 3, 2018, 6:36 pm
Background
Until recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced.

Objectives
To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK.

Methods
Two case–control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0–19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10–29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case–cohort analysis based on Cox regression.

Results
In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5–10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10–15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10–15 years after vaccination and 57% (95% CI 33% to 72%) 15–20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading.

Limitations
The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination.

Conclusions
Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading.

Author: Punam Mangtani
Posted: November 29, 2018, 9:15 am
Background
Until recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced.

Objectives
To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK.

Methods
Two case–control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0–19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10–29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case–cohort analysis based on Cox regression.

Results
In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5–10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10–15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10–15 years after vaccination and 57% (95% CI 33% to 72%) 15–20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading.

Limitations
The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination.

Conclusions
Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading.

Author: Punam Mangtani
Posted: November 26, 2018, 5:20 pm
People with pulmonary tuberculosis (TB) are at risk of developing chronic respiratory disorders due to residual lung damage. So far, the scope of the problem in high burden TB countries is relatively unknown.

Chronic respiratory symptoms (cough and phlegm lasting &gt;2 weeks) and radiological lung abnormalities were compared between adults with and without a history of TB among the general population of Uganda. Multivariable regression models were used to estimate odds ratios with adjustment for age, gender, smoking, education, setting and region. Random effects models accounted for village clustering effect.

Of 45,293 invited people from 70 villages, 41,154 (90.9%) participated in the survey. 798 had a history of TB and among them, 16% had respiratory symptoms and 41% x-ray abnormalities. Adjusted odds ratios showed strong evidence for individuals with a history of TB having increased risk of respiratory symptoms (OR=4·02, 95%CI: 3·25-4·96) and x-ray abnormalities (OR=17·52, 95%CI: 14·76-20·79); attributing 6% and 24% of the respective population risks.

In Uganda, a history of TB was a strong predictor of respiratory symptoms and lung abnormalities, before older age and smoking. Eliminating TB disease could reduce the prevalence of chronic respiratory symptoms as much as eliminating smoking.

Author: SC van Kampen
Posted: November 17, 2018, 3:09 pm
Tuberculosis (TB) is a disease of poverty. Ensuring access to health care without risk of financial hardship due to out-of-pocket health care expenditures (Universal Health Coverage; UHC) is essential for providing accessible care for underprivileged populations, but it is not enough.
The End TB Strategy promotes both patient-centred TB services and social protection measures, which aim to mitigate economic hardship on TB patients and their households due to direct medical and non-medical expenditures, as well as lost income. The Strategy includes a target that no families should face catastrophic total costs due to TB. The indicator linked to this target aims to capture the total economic burden linked to TB care, and thus differs from the “catastrophic expenditure on health” indicator, a key component of the UHC monitoring framework, aligned to the Sustainable Development Goals. Countries, especially high TB-burden countries, are expected to conduct nationally-representative TB patient cost surveys to establish baseline measurements for the catastrophic costs indicator. Findings from these surveys should also help identify entry points to develop policies to ensure better financial and social protection for TB patients. In this paper, we define the key measurable concepts for TB patient cost surveys, notably the types of costs that are captured and related affordability measures. We discuss the methods for measuring these notions in the UHC framework and contrast them with how they are measured in TB patient cost surveys.
Author: Debora Pedrazzoli
Posted: November 15, 2018, 1:38 pm
Migration is a key driver of tuberculosis (TB) in many low incidence settings, with the majority of TB cases attributed to reactivation of latent TB (LTBI) acquired overseas. A greater understanding of LTBI risk in heterogeneous migrant populations would aid health planning. We aimed to estimate the LTBI prevalence and distribution among local and overseas-born Australians.Annual risks of tuberculosis infection estimates were applied to population cohorts (by country of birth, year of arrival and age) in Australian census data in 2006, 2011 and 2016.Both the absolute number and proportion of Australian residents with LTBI increased – from 4.6% (IQR [interquartile range] 4.2-5.2%) in 2006 to 5.1% (IQR 4.7%-5.5%) in 2016 – due to the increasing proportion of the population born overseas (23.8% in 2006 to 28.3% in 2016). Of all residents estimated to have LTBI in 2016; 93.2% were overseas born, 21.6% were &lt;35 years of age and 34.4% had migrated to Australia since 2007.The overall prevalence of LTBI in Australia is low. Some residents, particularly migrants from high incidence settings, may have considerably higher risk of LTBI, and these findings allow for tailored public health interventions to reduce the risk and impact of future TB disease.
Author: KD Dale
Posted: October 30, 2018, 10:26 am
Evidence on the relative costs and effects of interventions that do not consider ‘real-world’ constraints on implementation may be misleading. However, in many low- and middle-income countries, time and data scarcity mean that incorporating health system constraints in priority setting can be challenging.

We developed a ‘proof of concept’ method to empirically estimate health system constraints for inclusion in model-based economic evaluations, using intensified case-finding strategies (ICF) for tuberculosis (TB) in South Africa as an example. As part of a strategic planning process, we quantified the resources (fiscal and human) needed to scale up different ICF strategies (cough triage and WHO symptom screening). We identified and characterised three constraints through discussions with local stakeholders: (1) financial constraint: potential maximum increase in public TB financing available for new TB interventions; (2) human resource constraint: maximum current and future capacity among public sector nurses that could be dedicated to TB services; and (3) diagnostic supplies constraint: maximum ratio of Xpert MTB/RIF tests to TB notifications. We assessed the impact of these constraints on the costs of different ICF strategies.

It would not be possible to reach the target coverage of ICF (as defined by policy makers) without addressing financial, human resource and diagnostic supplies constraints. The costs of addressing human resource constraints is substantial, increasing total TB programme costs during the period 2016-2035 by between 7% and 37% compared to assuming the expansion of ICF is unconstrained, depending on the ICF strategy chosen.

Failure to include the costs of relaxing constraints may provide misleading estimates of costs, and therefore cost-effectiveness. In turn, these could impact the local relevance and credibility of analyses, thereby increasing the risk of sub-optimal investments.

Author: FM Bozzani
Posted: October 15, 2018, 2:19 pm
The majority of tuberculosis transmission occurs in community settings. The primary aim of this study was to assess the association between exposure to community venues and multidrug-resistant tuberculosis (MDR-TB) disease. The secondary aim was to describe the social networks of MDR-TB cases and controls.

This case-control study was conducted in Lima, Peru. We recruited lab-confirmed MDR-TB cases and community controls matched on age and sex. Whole-genome sequencing was used to identify genetically-clustered cases. Venue-tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR-TB disease and person-time spent in community venues. A location-based social network was constructed with respondents connected if they reported frequenting the same venue and an exponential random graph model (ERGM) was fitted to model the network.

We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. Mean number of venues reported was similar in both groups (P=0.92). Cases reported spending more person-time (hours) in healthcare and transportation venues than controls (P&lt;0.05). Person-time in healthcare venues (Adjusted Odds Ratio (OR)=1.67, P=0.01), schools (OR=1.53, P&lt;0.01), and transportation (OR=1.25, P=0.03) was associated with MDR-TB disease. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected.

Exposure to healthcare venues, schools and transportation was associated with MDR-TB disease. Intervention across the segregated network of case venues may be necessary to effectively stem transmission.

Author: DP Bui
Posted: September 24, 2018, 2:58 pm
Background: With an estimated 10.4 million incident tuberculosis (TB) cases in 2015, and the current trajectory of 1.5%/year incidence rate decline, new TB vaccines are urgently needed to help meet the WHO goal of tuberculosis elimination by 2050. However, insufficient epidemiological evidence exists to inform TB vaccine development strategies and to assist clinical trial site selection and design. Research to meet these data needs is critical to accelerate TB vaccine development. To maximise the future impact of new TB vaccines, estimates of the population-level impact of vaccine characteristics and implementation strategies are needed to inform design of TB vaccine target product profiles. To accelerate and de-risk clinical trials, appropriate epidemiological data are required to inform trial site selection, sample size calculations and recruitment strategy. However, data availability at trial sites is limited, and prospective studies are resource-intensive, so new methods are needed to collect appropriate data to inform TB vaccine trial design.
To inform data-driven development strategies for new TB vaccines, the aims of this thesis were to 1) estimate the epidemiological impact of new TB vaccine characteristics and implementation in China to inform design of target product profiles; and 2) to develop a novel epidemiological spatial mapping tool capable of informing clinical trial design for new TB vaccines in low-income, high-burden settings.
Methods: A deterministic, age-structured, Mycobacterium tuberculosis transmission model was developed and calibrated to age-stratified epidemiological and demographic data from China. This was employed to estimate the population-level epidemiological impact of new TB vaccines over the 2025-2050 time horizon, through an exploration of potential vaccine characteristics and implementation strategies.
A new methodology for empirical data collection to determine spatial distribution of TB notifications was developed. The electronic PArticipant Locator application (ePAL app) combined 3,243 community-identified points of interest with high resolution satellite maps, within an electronic tablet-based case report form. The app was integrated in to the National Tuberculosis Programme in Blantyre, Malawi, for collection of demographics, health status and coordinates of place of residence for patients ≥18 years initiating TB treatment. Accuracy of ePAL-recorded co-ordinates was evaluated against GPS coordinates obtained at the participant’s place of residence.
Results: Mathematical modelling predicted a shift towards a reactivation-driven, ageing TB epidemic in China by 2050. Vaccines protective against disease, effective post-infection and providing at least 5 years protection were essential for achieving higher levels of impact. Vaccination of older adults provided greater population-level impact than vaccinating adolescents for all equivalent vaccines explored, even if much lower coverage were achieved in older adult vaccination. Recommendations for post-infection vaccines were robust to substantial reductions in efficacy and duration of protection in older adults, whereas for pre-infection vaccines in some of these scenarios adolescent vaccination may be equivalent or preferred. Vaccinating older adults with post-infection vaccines provided substantially higher impact than pre-infection vaccines.
1,899 TB patients were registered using ePAL in the 12-month study period, with high patient acceptance (98.7%, 1,899/1,924). ePAL achieved clinic-based collection of patient location of residence accurate to a median of 84 metres (IQR: 35-317 metres) in a high population density urban setting without a municipal address system. Advantages of the ePAL system included real-time availability of high-resolution spatial data, low set up costs, and ease of use by health staff as part of routine TB registration. Data were used to identify areas with high TB burden, potentially suitable for TB vaccine trials.
Conclusions: The research presented in this thesis informs the development of appropriate TB vaccines and target populations to maximise future population-level impact. A prevention of disease vaccine efficacious post-infection and delivered to older adults would contribute towards maximising population-level impact in China. Adolescent-targeted tuberculosis vaccines are likely to have low impact in ageing, reactivation-driven epidemics like China, which suggests a modification of the current strategic focus on adolescents among certain funders. Clinical trials should assess disease endpoints, include M.tb-infected and older adult populations, and extend beyond the usual 2-3 years follow up. To support design of disease endpoint trials, ePAL may provide an accurate, easily implementable, low-cost tool for identification of areas of high TB burden in settings without addresses.
Author: RC Harris
Posted: August 23, 2018, 2:54 pm
Mixed, polyclonal Mycobacterium tuberculosis infection occurs in natural populations. Developing an effective method for detecting such cases is important in measuring the success of treatment and reconstruction of transmission between patients. Using whole genome sequence (WGS) data, we assess two methods for detecting mixed infection: (i) a combination of the number of heterozygous sites and the proportion of heterozygous sites to total SNPs, and (ii) Bayesian model-based clustering of allele frequencies from sequencing reads at heterozygous sites.

In silico and in vitro artificially mixed and known pure M. tuberculosis samples were analysed to determine the specificity and sensitivity of each method. We found that both approaches were effective in distinguishing between pure strains and mixed infection where there was relatively high (&gt; 10%) proportion of a minor strain in the mixture. A large dataset of clinical isolates (n = 1963) from the Karonga Prevention Study in Northern Malawi was tested to examine correlations with patient characteristics and outcomes with mixed infection. The frequency of mixed infection in the population was found to be around 10%, with an association with year of diagnosis, but no association with age, sex, HIV status or previous tuberculosis.

Mixed Mycobacterium tuberculosis infection was identified in silico using whole genome sequence data. The methods presented here can be applied to population-wide analyses of tuberculosis to estimate the frequency of mixed infection, and to identify individual cases of mixed infections. These cases are important when considering the evolution and transmission of the disease, and in patient treatment.

Author: B Sobkowiak
Posted: August 17, 2018, 8:37 am
HIV and tuberculosis (TB) remain leading causes of preventable death in low- and middle-income countries (LMICs). The World Health Organization (WHO) recommends HIV testing for all individuals with TB symptoms, but implementation has been suboptimal. We conducted a systematic literature review and meta-analyses to estimate HIV and TB prevalence, and short-term (two to six months) mortality, among adults with TB symptoms at community- and facility level.

We searched Embase, Global Health and MEDLINE databases, and reviewed conference abstracts for studies reporting simultaneous HIV and TB screening of adults in LMICs published between January 2003 and December 2017. Meta-analyses were performed to estimate prevalence of HIV, undiagnosed TB and mortality risk at different health system levels.

Sixty-two studies including 260,792 symptomatic adults were identified, mostly from Africa and Asia. Median HIV prevalence was 19.2% (IQR: 8.3% to 40.4%) at community level, 55.7% (IQR: 20.9% to 71.2%) at primary care level and 80.7% (IQR: 73.8% to 84.6%) at hospital level. Median TB prevalence was 6.9% (IQR: 3.3% to 8.4%) at community, 20.5% (IQR: 11.7% to 46.4%) at primary care and 36.4% (IQR: 22.9% to 40.9%) at hospital level. Median short-term mortality was 22.6% (IQR: 15.6% to 27.7%) among inpatients, 3.1% (IQR: 1.2% to 4.2%) at primary care and 1.6% (95% CI: 0.45 to 4.13, n = 1 study) at community level.

Adults with TB symptoms have extremely high prevalence of HIV infection, even when identified through community surveys. TB prevalence and mortality increased substantially at primary care and inpatient level respectively. Strategies to expand symptom-based TB screening combined with HIV and TB testing for all symptomatic individuals should be of the highest priority for both disease programmes in LMICs with generalized HIV epidemics. Interventions to reduce short-term mortality are urgently needed.

Author: M Nliwasa
Posted: August 2, 2018, 11:33 am
To find the millions of missed tuberculosis (TB) cases, national TB programmes are under pressure to expand TB disease screening, and target populations with lower disease prevalence. Together with imperfect performance and application of existing diagnostic tools, including empirical diagnosis, broader screening risks placing individuals without TB on prolonged treatment. These false-positive diagnoses have profound consequences for TB patients and prevention efforts, yet are usually overlooked in policy decision-making.In this paper we describe the pathways to a false-positive TB diagnosis, including trade-offs involved in the development and application of diagnostic algorithms. We then consider the wide range of potential consequences for individuals, households, health systems, and reliability of surveillance data. Finally, we suggest practical steps that the TB community can take to reduce the frequency and potential harms of false-positive TB diagnosis and to more explicitly assess the trade-offs involved in the screening and diagnostic process.
Author: RMGJ Houben
Posted: July 12, 2018, 11:40 am
Tackling the social determinants of Tuberculosis (TB) through social protection is a key element of the post-2015 End TB Strategy. However, evidence informing policies are still scarce. Mathematical modelling has the potential to contribute to fill this knowledge gap, but existing models are inadequate. The S-PROTECT consortium aimed to develop an innovative mathematical modelling approach to better understand the role of social protection to improve TB care, prevention and control.

S-PROTECT used a three-steps approach: 1) the development of a conceptual framework; 2) the extraction from this framework of three high-priority mechanistic pathways amenable for modelling; 3) the development of a revised version of a standard TB transmission model able to capture the structure of these pathways. As a test case we used the Bolsa Familia Programme (BFP), the Brazilian conditional cash transfer scheme.

Assessing one of these pathways, we estimated that BFP can reduce TB prevalence by 4% by improving households income and thus their nutritional status. When looking at the direct impact via malnutrition (not income mediated) the impact was 33%. This variation was due to limited data availability, uncertainties on data transformation and the pathway approach taken. These results are preliminary and only aim to serve as illustrative example of the methodological challenges encountered in this first modelling attempt, nonetheless they suggest the potential added value of integrating TB standard of care with social protection strategies.

Results are to be confirmed with further analysis. However, by developing a generalizable modelling framework, S-PROTECT proved that the modelling of social protection is complex, but doable and allowed to draw the research road map for the future in this field.

Author: D Boccia
Posted: July 3, 2018, 1:20 am
Globally, men have a higher epidemiological burden of tuberculosis (incidence, prevalence, mortality) than women, possibly due to differences in disease incidence, treatment initiation, self-cure and/or untreated-tuberculosis mortality rates. Using a simple, gender-stratified compartmental model, we employed a Bayesian approach to explore which factors most likely explain men’s higher burden. We applied the model to smear-positive pulmonary tuberculosis in Viet Nam (2006-07) and Malawi (2013-14). Posterior estimates were consistent with gender-specific prevalence and notifications in both countries. Results supported higher incidence in men and showed that both genders faced longer durations of untreated disease than estimated by self-reports. Prior untreated disease durations were revised upwards 8- to 24-fold, to 2.2 (95% credible interval: 1.7, 2.9) and 2.8 (1.8, 4.1) years for men in Viet Nam and Malawi, respectively, approximately a year longer than for women in each country. Results imply that substantial gender differences in tuberculosis burden are almost solely attributable to men’s disadvantages in disease incidence and untreated disease duration. The latter, for which self-reports provide a poor proxy, implies inadequate coverage of case finding strategies. These results highlight an urgent need for better understanding of gender-specific barriers faced by men and support the systematic targeting of men for screening.
Author: KC Horton
Posted: July 3, 2018, 1:18 am
Global tuberculosis (TB) targets were set as part of the World Health Organization’s End TB Strategy (2016-2035) and the Sustainable Development Goals (2016-2030).

To define and explain the rationale for these targets.

Scenarios for plausible reductions in TB deaths and cases were developed using empirical evidence from best-performing countries and modelling of the scale-up of under-used interventions and hypothetical TB vaccines. Results were discussed at consultations in 2012 and 2013. A final proposal was presented to the World Health Assembly in 2014 and unanimously endorsed by all Member States.

The 2030 targets are a 90% reduction in TB deaths and 80% reduction in TB incidence compared with 2015 levels. The 2035 targets are for reductions of 95% and 90%, respectively. A third target-that no TB-affected households experience catastrophic costs due to the disease by 2020-was also agreed.

The global TB targets and milestones set for the period 2016-2035 are ambitious. Achieving them requires concerted action on several fronts, but two things are fundamental: 1) progress towards universal health coverage to ensure that everyone with TB can access high-quality treatment; and 2) substantial investment in research and development for new tools to prevent TB disease among the approximately 1.7 billion people infected.

Author: K Floyd
Posted: June 26, 2018, 1:22 am
Tuberculosis (TB) is known as a disease of the poor. Despite TB diagnosis and care usually being offered for free, TB patients can still face substantial costs, especially in the context of multi-drug resistance (MDR). The End TB Strategy calls for zero TB-affected families incurring &quot;catastrophic&quot; costs due to TB by 2025. This paper examines, by MDR status, the level and composition of costs incurred by TB-affected households during care seeking and treatment; assesses the affordability of TB care using catastrophic and impoverishment measures; and describes coping strategies used by TB-affected households to pay for TB care.

A nationally representative survey of TB patients at public health facilities across Ghana.

We enrolled 691 patients (66 MDR). The median expenditure for non-MDR TB was US$429.6 during treatment, vs. US$659.0 for MDR patients (p-value=0.001). Catastrophic costs affected 64.1% of patients. MDR patients were pushed significantly further over the threshold for catastrophic payments than DS patients. Payments for TB care led to a significant increase in the proportion of households in the study sample that live below the poverty line at the time of survey compared to pre-TB diagnosis. Over half of patients undertook coping strategies.

TB patients in Ghana incur substantial costs, despite free diagnosis and treatment. High rates of catastrophic costs and coping strategies in both non-MDR and MDR patients show that new policies are urgently needed to ensure TB care is actually affordable for TB patients. This article is protected by copyright. All rights reserved.

Author: D Pedrazzoli
Posted: June 6, 2018, 1:59 pm
National Tuberculosis Programmes (NTPs) require specialist input to support the development of policy and practice informed by evidence, typically against tight deadlines.

To describe lessons learned from establishing a dedicated tuberculosis (TB) think tank to advise the South African NTP on TB policy.

A national TB think tank was established to advise the NTP in support of evidence-informed policy. Support was provided for activities, including meetings, modelling and regular telephone calls, with a wider network of unpaid expert advisers under an executive committee and working groups. Intervention evaluation used desktop analysis of documentary evidence, interviews and direct observation.

The TB Think Tank evolved over time to acquire three key roles: an ‘institution’, a ‘policy dialogue forum’ and an ‘interface’. Although enthusiasm was high, motivating participation among the NTP and external experts proved challenging. Motivation of working groups was most successful when aligned to a specific need for NTP decision making. Despite challenges, the TB Think Tank contributed to South Africa’s first ever TB and human immunodeficiency virus (HIV) investment case, and the decision to create South Africa’s first ever ring-fenced grant for TB. The TB Think Tank also assisted the NTP in formulating strategy to accelerate progress towards reaching World Health Organization targets.

With partners, the TB Think Tank achieved major successes in supporting evidence-informed decision making, and garnered increased funding for TB in South Africa. Identifying ways to increase the involvement of NTP staff and other experts, and keeping the scope of the Think Tank well defined, could facilitate greater impact. Think tank initiatives could be replicated in other settings to support evidence-informed policy making.

Author: RG White
Posted: June 6, 2018, 1:46 pm
Little is known about the impact of growing migration on the pattern of tuberculosis (TB) transmission in middle-income countries. We estimated TB recent transmission and its associated factors and investigated the presence of cross-transmission between South American migrants and Brazilians.

We studied a convenient sample of cases of people with pulmonary TB in a central area of São Paulo, Brazil, diagnosed between 2013 and 2014. Cases with similar restriction fragment length polymorphism (IS6110-RFLP) patterns of their Mycobacterium tuberculosis complex isolates were grouped in clusters (recent transmission). Clusters with both Brazilian and South American migrants were considered mixed (cross-transmission). Risk factors for recent transmission were studied using logistic regression.

Isolates from 347 cases were included, 76.7% from Brazilians and 23.3% from South American migrants. Fifty clusters were identified, which included 43% South American migrants and 60.2% Brazilians (odds ratio = 0.50, 95% confidence interval = 0.30-0.83). Twelve cross-transmission clusters were identified, involving 24.6% of all clustered cases and 13.8% of all genotyped cases, with migrants accounting for either an equal part or fewer cases in 11/12 mixed clusters.

Our results suggest that TB disease following recent transmission is more common among Brazilians, especially among those belonging to high-risk groups, such as drug users. Cross-transmission between migrants and Brazilians was present, but we found limited contributions from migrants to Brazilians in central areas of São Paulo and vice versa.

Author: JM Pescarini
Posted: May 8, 2018, 1:16 am
Contact tracing is a key part of tuberculosis prevention and care, aiming to hasten diagnosis and prevent transmission. The proportion of case-contact pairs for which recent transmission occurred and the typical timespans between the index case and their contact accessing care are not known; we aimed to calculate these. We analysed individual-level TB contact tracing data, collected in London from 20/01/2011-31/12/2015, linked to tuberculosis surveillance and MIRU-VNTR 24-locus strain-typing information. Of pairs of index cases and contacts diagnosed with active tuberculosis, 85/314 (27%) had strain typing data available for both. Of these pairs, 79% (67/85) shared indistinguishable isolates, implying probable recent transmission. Of pairs in which both contact and the index case had a social risk factor, 11/11 (100%) shared indistinguishable isolates, compared to 55/75 (75%) of pairs in which neither had a social risk factor (P = 0.06). The median time interval between the index case and their contact accessing care was 42 days (IQR: 16, 96). As over 20% of pairs did probably not involve recent transmission between index case and contact, the effectiveness of contact tracing is not necessarily limited to those circumstances where the index case has transmitted disease to their close contacts.
Author: SM Cavany
Posted: May 3, 2018, 1:16 am

 

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