Tuberculosis Control Strategies Research Articles

Mycobacterium tuberculosis-Secreted Tyrosine Phosphatases as Targets Against Tuberculosis: Exploring Natural Sources in Searching for New Drugs.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which primarily affects the respiratory tract. Combinations of drugs are used for therapeutic synergism and to prevent the emergence of drug resistant strains, but even first- or secondchoice drugs present some disadvantages, such as significant side effects and the need for long duration of treatments. Thus, new strategies for TB control and treatment are highly demanded. In this context, protein tyrosine phosphatases (PtpA and PtpB) are secreted by Mtb within the host macrophage and they have been shown to contribute to Mtb pathogenicity. The understanding of the role of these PTPs has led to interesting anti-TB drugs discovery. Here, we review the current knowledge on these two proteins as targets for novel anti-TB therapies, with particular emphasis on their mechanism of action and current advancements in developing small molecule inhibitors from natural sources.

Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.

BackgroundTimely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB) in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai.MethodsA population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values.ResultsThe mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days) and retreatment patients (25 days). Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation.ConclusionAchieving positive behavioural changes in providers (especially non-allopaths) and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of point of care diagnostics would be singularly effective in curbing pathway delays.

Time-series analysis of monthly age-specific numbers of newly registered cases of active tuberculosis in Japan from 1998 to 2013.

We investigated the seasonality of age-specific tuberculosis (TB) in Japan. To allow the development of TB control strategies for different age groups we used a time-series analysis, including a spectral analysis and least squares method, to analyse the monthly age-specific numbers of newly registered cases of all forms of active TB in Japan from January 1998 to December 2013. The time-series data are reported in 10-year age groups: 0-9, 10-19, …, 70-79, and ⩾80 years. We defined the contribution ratio of the 1-year cycle, Q 1, as the contribution of the amplitude of a 1-year cycle to the whole amplitude of the time-series data. The Q 1 values in the age groups corresponding to adolescence and middle life (10-39 years) and old age (⩾70 years) were high. The peaks in the active TB epidemics for the ⩾70 years age group occurred in August and September, 1-2 months behind the peaks for the 10-39 years age group (June and July). An active TB epidemic might be attributable to travel by public transport and irregular employment in the 10-39 years age group and immune system suppression by low winter temperatures in the ⩾70 years age group.

Tuberculosis in native- and foreign-born populations in Portugal.

Tuberculosis (TB) is a major global health problem, and during the last 20 years, industrialised countries have shown similar patterns in TB notifications: decreasing TB incidence in native populations and increasing incidence in foreign-born populations. To characterise risk factors associated with TB among native- and foreign-born TB patients in Portugal and identify barriers to the management of foreign cases. Analysis of the data from the national tuberculosis surveillance system and data from an online survey of physicians managing TB cases in the country. Risk factors in the two populations differed. Foreign-born patients were younger, less likely to use drugs or alcohol and had fewer comorbidities. They were also more likely to be human immunodeficiency virus positive, to be employed and to be homeless/living in shelters. The outcome of the disease and the time to diagnosis were not significantly different between the two populations. The most important barriers to the management of foreign-born TB cases were language and fear of deportation. As there are significant differences between the two populations, different TB control strategies should be implemented in the two populations.

Environmental Presence of Mycobacterium tuberculosis Complex in Aggregation Points at the Wildlife/Livestock Interface.

The members of the Mycobacterium tuberculosis complex (MTC) cause tuberculosis (TB). Infection is transmitted within and between livestock and wildlife populations, thus hampering TB control. Indirect transmission might be facilitated if MTC bacteria persist in the environment long enough to represent a risk of exposure to different species sharing the same habitat. We have, for the first time, addressed the relationship between environmental MTC persistence and the use of water resources in two TB endemic areas in southern Spain with the objective of identifying the presence of environmental MTC and its driving factors at ungulates' water aggregation points. Camera-trap monitoring and MTC diagnosis (using a new MTC complex-specific PCR technique) were carried out at watering sites. Overall, 55.8% of the water points tested positive for MTC in mud samples on the shore, while 8.9% of them were positive in the case of water samples. A higher percentage of MTC-positive samples was found at those waterholes where cachectic animals were identified using camera-trap monitoring, and at the smallest waterholes. Our results help to understand the role of indirect routes of cross-species TB transmission and highlight the importance of certain environmental features in maintaining infection in multihost systems. This will help to better target actions and implement control strategies for TB at the wildlife/livestock interface.

Abrupt Decline in Tuberculosis among Foreign-Born Persons in the United States

While the number of reported tuberculosis (TB) cases in the United States has declined over the past two decades, TB morbidity among foreign-born persons has remained persistently elevated. A recent unexpected decline in reported TB cases among foreign-born persons beginning in 2007 provided an opportunity to examine contributing factors and inform future TB control strategies. We investigated the relative influence of three factors on the decline: 1) changes in the size of the foreign-born population through immigration and emigration, 2) changes in distribution of country of origin among foreign-born persons, and 3) changes in the TB case rates among foreign-born subpopulations. Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined TB case counts, TB case rates, and population estimates, stratified by years since U.S. entry and country of origin. Regression modeling was used to assess statistically significant changes in trend. Among foreign-born recent entrants (<3 years since U.S. entry), we found a 39.5% decline (-1,013 cases) beginning in 2007 (P<0.05 compared to 2000–2007) and ending in 2011 (P<0.05 compared to 2011–2014). Among recent entrants from Mexico, 80.7% of the decline was attributable to a decrease in population, while the declines among recent entrants from the Philippines, India, Vietnam, and China were almost exclusively (95.5%–100%) the result of decreases in TB case rates. Among foreign-born non-recent entrants (≥3 years since U.S. entry), we found an 8.9% decline (-443 cases) that resulted entirely (100%) from a decrease in the TB case rate. Both recent and non-recent entrants contributed to the decline in TB cases; factors contributing to the decline among recent entrants varied by country of origin. Strategies that impact both recent and non-recent entrants (e.g., investment in overseas TB control) as well as those that focus on non-recent entrants (e.g., expanded targeted testing of high-risk subgroups among non-recent entrants) will be necessary to achieve further declines in TB morbidity among foreign-born persons.

Effect of culling and vaccination on bovine tuberculosis infection in a European badger (Meles meles) population by spatial simulation modelling

The control of bovine tuberculosis (bTB) in cattle herds in the Republic of Ireland (ROI) is partially hindered by spill-back infection from wild badgers (Meles meles). The aim of this study was to determine the relative effects of interventions (combinations of culling and/or vaccination) on bTB dynamics in an Irish badger population. A spatial agent-based stochastic simulation model was developed to evaluate the effect of various control strategies for bovine tuberculosis in badgers: single control strategies (culling, selective culling, vaccination, and vaccine baits), and combined strategies (Test vaccinate/cull (TVC)), split area approaches using culling and vaccination, or selective culling and vaccination, and mixed scenarios where culling was conducted for five years and followed by vaccination or by a TVC strategy. The effect of each control strategy was evaluated over a 20-year period. Badger control was simulated in 25%, 50%, and 75% area (limited area strategy) or in the entire area (100%, wide area strategy). For endemic bTB, a culling strategy was successful in eradicating bTB from the population only if applied as an area-wide strategy. However, this was achieved only by risking the extinction of the badger population. Selective culling strategies (selective culling or TVC) mitigated this negative impact on the badger population’s viability. Furthermore, both strategies (selective culling and TVC) allowed the badger population to recover gradually, in compensation for the population reduction following the initial use of removal strategies. The model predicted that vaccination can be effective in reducing bTB prevalence in badgers, when used in combination with culling strategies (i.e. TVC or other strategies). If fecundity was reduced below its natural levels (e.g. by using wildlife contraceptives), the effectiveness of vaccination strategies improved. Split-area simulations highlighted that interventions can have indirect effects (e.g. on population size) in non-treatment areas. Our model suggests that mixed control strategies could maintain infection prevalence to a low level for a considerable period even with a growing population. The model supported the hypothesis that culling strategies appeared to be the most effective method for the control of bTB in badgers using parameters, where available, from ROI, either singly or in combination with other strategies. In this model, the success of a vaccination strategy depended partially upon population density and the proportion of the population infected, therefore an initial culling program (to reduce density and/or remove infected badgers) followed by long-term vaccination may be effective in controlling bTB in badgers.

Host and Microbial Predictors of Childhood Extrathoracic Tuberculosis and Tuberculosis Meningitis.

Childhood tuberculosis (TB) is a major infectious disease causing morbidity and mortality in children and yet has been largely ignored until recently. This study is the first study to characterize childhood TB in China incorporating both Mycobacterium tuberculosis genetic characteristics and patient data. We analyzed a total of 331 culture-confirmed childhood TB cases and 158 M. tuberculosis isolates from a subset of the study sample. Univariate and multivariate logistic regression analyses were performed to identify host and microbial predictors for having extrathoracic TB alone, concurrent thoracic and extrathoracic TB and TB meningitis (TBM), respectively. Fifty-eight percent (192/331) of the study subjects had extrathoracic TB, and 139 (42.0%) cases had TBM. Both age of less than 5 years [adjusted odds ratio (OR): 4.52; 95% confidence interval (CI): 1.27-16.16] and female sex (adjusted OR: 2.72; 95% CI: 1.03-7.18) were significantly associated with extrathoracic TB alone, whereas living in rural area (adjusted OR: 2.35; 95% CI: 1.06-5.18) was significantly associated with thoracic-extrathoracic TB. Age of less than 5 years was also strongly associated with TBM (adjusted OR: 3.63; 95% CI: 1.64-8.05). Sixty-four percent (101/158) of the study isolates were Beijing lineage strains. Infection with Beijing lineage strains was significantly associated with thoracic-extrathoracic TB (adjusted OR: 2.39; 95% CI: 1.11-5.15) and TBM (adjusted OR: 2.25; 95% CI: 1.10-4.60). Both microbial and host factors can affect the outcome of M. tuberculosis infection in children. Future studies incorporating host and pathogen data from different populations are warranted to develop new strategies for childhood TB control.

A new strategy for tuberculosis control in North Korea.

Tuberculosis is one of the most prevalent diseases in North Korea. Despite some positive accomplishments by current aid projects, it is still necessary to investigate the existing aid system. The following are necessary for improvement: sustaining a high degree of expertise, cooperation among various related parties including the international community, mediation to induce this cooperation, a more active role of the South Korean government, and encouragement of North Korea to more actively participate. Achieving these will help solve the issues of current tuberculosis aid projects in North Korea and lead to more successful outcomes.

Managementul infecţiei latente cu tuberculoză în România – limite şi perspective

In 2014 the World Health Organization adopted a new strategy for tuberculosis control – infectious disease with the highest mortality in the world after AIDS. This new strategy – The End TB Strategy – is aimed to reducing tuberculosis disease by 90% and tuberculosis mortality by 95%, so that by 2035 TB is no longer considered a problem global public health. The World Health Organization report on tuberculosis published in 2014 is estimated that about one third of the world population is infected with M. tuberculosis (approx. 2 billion); 5-10% of them will develop active disease, thus fullfiling the TB pandemia. It is therefore an essential objective to diagnose these cases of latent tuberculosis infection and to establish precise criteria of the latent TB infection treatment. Tuberculin skin test is the most important test for emphasis of TB infection in an organism. The results obtained in recent years in mycobacterial genomics and human cell immunology have led to the development of other tests that detect tuberculosis infection, of which the most commonly used is the test that measures the release of IFN-γ (Interferon gamma-releasing assay IGRA). Any patient with increased risk of infection to disease progression and who has a positive skin test is a candidate for treatment. Immuno-compromised patients (HIV infected, treatment with anti-TNF, organ transplantation, immunosuppressive medication) with LTBI have a higher risk of reactivation. Immuno-compromised patients with LTBI should receive treatment.

Does treatment collection and observation each day keep the patient away? An analysis of the determinants of adherence among patients with Tuberculosis in South Africa

Directly observed treatment short course (DOTS) has been the recommended strategy for Tuberculosis (TB) control since 1995. Developed as an alternative to inpatient treatment, it involves observation of patients' medication intake to promote adherence. However, the burden of daily clinic visits may affect access to care. Using a mixed methods approach, we consider whether (1) non-adherence differs systematically between patients required to make daily clinic visits and patients cared for under less frequent clinic visits and (2) the association between frequency of required clinic visits and adherence depends on affordability and acceptability of care. Data were collected in facility exit interviews with 1200 TB patients in two rural and two urban sub-districts in South Africa. Additionally, 17 in-depth interviews were completed with TB patients. After controlling for socioeconomic and demographic factors, patient type (new or retreatment) and treatment duration, regression analyses showed that daily attending patients were over twice as likely to report a missed clinic visit (P < 0.001) or a missed dose of treatment (P = 0.002) compared with patients required to attend clinics for treatment collection less frequently. Missed visits increased with treatment duration (P = 0.01). The significant interaction between clinic visit frequency and treatment duration indicated that sustaining daily visits over time may become increasingly difficult over the course of treatment. The qualitative analysis identified treatment cost and duration, patients' physical condition and varying social contexts (family, community and work) as important influences on adherence. These findings suggest that strategies involving daily clinic visits may require reconsideration if resources for TB care are to be used efficiently. The adoption of approaches that place patient interests at the centre of TB treatment delivery would appear to be of high priority, particularly in countries where TB prevalence is high and resources for TB care are highly constrained.

MicroRNA signatures from multidrug‑resistant Mycobacterium tuberculosis.

Tuberculosis (TB) infections, caused by multi-drug-resistant Mycobacterium tuberculosis (MDR MTB), remain a significant public health concern worldwide. The regulatory mechanisms underlying the emergence of MDR MTB strains remain to be fully elucidated, and further investigation is required in order to develop better strategies for TB control. The present study investigated the expression profile of microRNA (miRNA) in MTB strains, and examined the differences between sensitive MTB and MDR MTB using next generation sequencing (NGS) with Illumina Deep Sequencing technology to better understand the mechanisms of resistance in MDR MTB, A total of 5, 785 and 195, and 6, 290 and 595 qualified Illumina reads were obtained from two MDR MTB strains, and 6, 673 and 665, and 7, 210 and 217 qualified Illumina reads were obtained from two sensitive MTB strains. The overall de novo assembly of miRNA sequence data generated 62 and 62, and 95 and 112 miRNAs between the 18 and 30 bp long from sensitive MTB strains and MDR MTB strains, respectively. Comparative miRNA analysis revealed that 142 miRNAs were differentially expressed in the MDR MTB strain, compared with the sensitive MTB strain, of which 48 were upregulated and 94 were downregulated. There were six similarly expressed miRNAs between the MDR and sensitive MTB strains, and 108 miRNAs were expressed only in the MDR MTB strain. The present study acquired miRNA data from sensitive MTB and MDR MTB strains using NGS techniques, and this identification miRNAs may serve as an invaluable resource for revealing the molecular basis of the regulation of expression associated with the mechanism of drug-resistance in MTB.

Current status of Bacille Calmette Guérin (BCG) immunisation in Europe – A ptbnet survey and review of current guidelines

BackgroundThe incidence of tuberculosis (TB) and the use of Bacille Calmette-Guérin (BCG) vaccines differ significantly worldwide. Information regarding recent changes in BCG use and immunisation policies is difficult to access. Therefore, this study aimed to systematically collect up-to-date data on the use of BCG in Europe. MethodsA web-based survey of members of the Paediatric Tuberculosis Network European Trials group (ptbnet) and Tuberculosis Network European Trials group (TBnet) was conducted between October 2012 and May 2013. ResultsA total of 89 individuals from 31 European countries participated. Participants from 27/31 (87%) countries reported to have a national BCG immunisation policy/guideline. Reported indications for BCG immunisation were: universally at birth (14/31; 45%), universally at older age (2/31; 6%), at birth for high-risk groups (12/31; 39%), at older age for high-risk groups (6/31; 19%), at older age for Mantoux-negative individuals (6/31;19%), for immigrants (4/31; 13%) and as a travel vaccine (10/31; 32%). Members from 11 (35%) countries reported changes in BCG policies in the previous 5 years: discontinuation of universal immunisation of infants/children (6/11), reintroduction of immunisation of high-risk children (3/11), and change in BCG vaccine strain (2/11). Members from 24/31 (77%) countries reported using BCG Denmark. ConclusionsImmunisation policies regarding BCG vaccine exist in the majority of European countries. Indications for BCG immunisation varied considerably, likely reflecting national TB incidence rates, immigration and other factors influencing TB control strategies. Importantly, the considerable number of recent policy changes highlights the need for regular collection of up-to-date information to inform public health planning.

National tuberculosis prevalence surveys in Asia, 1990-2012: an overview of results and lessons learned.

In many countries, national tuberculosis (TB) prevalence surveys are the only way to reliably measure the burden of TB disease and monitor trends. They can also provide evidence about the current performance of TB care and control and how this could be improved. We developed an inventory of Asian surveys from 1953 to 2012 and then compiled and analysed a standard set of data for all national surveys implemented between 1990 (the baseline year for 2015 global TB targets) and 2012. There were 21 surveys in 12 countries between 1990 and 2012; published results were available for 18. The participation rate was at least 80% and often much higher except for two surveys in Thailand. The prevalence of bacteriologically-positive TB disease among adults aged ≥15years varied widely among countries (1.2 per 1000 population in China in 2010 to 15 per 1000 population in Cambodia in 2002), but age and sex distribution patterns were consistent with a progressive increase in rates of disease by age, and men accounting for 66-75% of prevalent cases. A high proportion of cases (40-79% across all surveys) did not report TB symptoms that met screening criteria (generally cough of 2-3weeks or more, and blood in the sputum) and were only detected due to chest X-ray screening of all survey participants; this proportion increased over time in countries with repeat survey data. The ratio of prevalent cases to cases notified to national TB programmes was typically around two, but was as high as three in Lao PDR and Pakistan even after the internationally recommended TB control strategy had been implemented nationwide for several years. Four countries (China, Cambodia, the Republic of Korea and the Philippines demonstrated declines in smear or culture-positive pulmonary TB prevalence of approximately 50% over 10years. National TB prevalence surveys in Asia show that large reductions in the prevalence of TB disease can be achieved within a decade, that men bear much more of the burden than women and that the epidemic is ageing. Comparisons among countries show that more can be achieved in TB control in some countries with existing strategies and technologies. However, with many prevalent cases not reporting classic TB symptoms, all countries face the challenge of defining and implementing strategies that will result in earlier detection and treatment of cases.

Testing Eurasian wild boar piglets for serum antibodies against Mycobacterium bovis

Animal tuberculosis (TB) caused by infection with Mycobacterium bovis and closely related members of the M. tuberculosis complex (MTC), is often reported in the Eurasian wild boar (Sus scrofa). Tests detecting antibodies against MTC antigens are valuable tools for TB monitoring and control in suids. However, only limited knowledge exists on serology test performance in 2–6 month-old piglets. In this age-class, recent infections might cause lower antibody levels and lower test sensitivity. We examined 126 wild boar piglets from a TB-endemic site using 6 antibody detection tests in order to assess test performance. Bacterial culture (n=53) yielded a M. bovis infection prevalence of 33.9%, while serum antibody prevalence estimated by different tests ranged from 19% to 38%, reaching sensitivities between 15.4% and 46.2% for plate ELISAs and between 61.5% and 69.2% for rapid immunochromatographic tests based on dual path platform (DPP) technology. The Cohen kappa coefficient of agreement between DPP WTB (Wildlife TB) assay and culture results was moderate (0.45) and all other serological tests used had poor to fair agreements. This survey revealed the ability of several tests for detecting serum antibodies against the MTC antigens in 2–6 month-old naturally infected wild boar piglets. The best performance was demonstrated for DPP tests. The results confirmed our initial hypothesis of a lower sensitivity of serology for detecting M. bovis-infected piglets, as compared to older wild boar. Certain tests, notably the rapid animal-side tests, can contribute to TB control strategies by enabling the setup of test and cull schemes or improving pre-movement testing. However, sub-optimal test performance in piglets as compared to that in older wild boar should be taken into account.

"Impact of and response to increased tuberculosis prevalence among Syrian refugees compared with Jordanian tuberculosis prevalence: case study of a tuberculosis public health strategy".

IntroductionBy the summer of 2014, the Syrian crisis resulted in a regional humanitarian emergency with 2.9 million refugees, including 608,000 in Jordan. These refugees access United Nations High Commissioner for Refugees (UNHCR)-sponsored clinics or Jordan Ministry of Health clinics, including tuberculosis diagnosis and treatment. Tuberculosis care in Syria has deteriorated with destroyed health infrastructure and drug supply chain. Syrian refugees may have undiagnosed tuberculosis; therefore, the UNHCR, the International Organization for Migration (IOM), the National Tuberculosis Program (NTP), and the Centers for Disease Control and Prevention developed the Public Health Strategy for Tuberculosis among Syrian Refugees in Jordan. This case study presents that strategy, its impact, and recommendations for other neighboring countries.Case descriptionUNHCR determined that World Health Organization (WHO) criteria for implementing a tuberculosis program in an emergency were met for the Syrian refugees in Jordan. Jordan NTP assessed their tuberculosis program and found that access to Syrian refugees was the one component of their program missing. Therefore, a strategy for tuberculosis control among Syrian refugees was developed. Since that development through work with IOM, UNHCR, and NTP, tuberculosis case detection among Syrian refugees is almost 40 % greater (74 cases/12 months or 1.01/100,000 monthly through June 2014 vs. 56 cases/16 months or 0.73/100,000 monthly through June 2013) using estimated population figures; more than two fold the 2012 Jordan tuberculosis incidence. Additionally, the WHO objective of curing ≥85 % of newly identified infectious tuberculosis cases was met among Syrian refugees.Discussion and evaluationTuberculosis (TB) rates among displaced persons are high, but increased detection is possible. High TB rates were found among Syrian refugees through active screening and will probably persist as the Syrian crisis continues. Active screening can detect tuberculosis early and reduce risk for transmission. However, this strategy needs sustainable funding to continue and all activities have not been realized.ConclusionsInitial assessment found that tuberculosis among Syrian refugees was at a high incidence rate. Through partnership, a cohesive Jordanian tuberculosis strategy was developed for Syrian refugees and it has potential to inform treatment and control efforts for other regional countries impacted by the Syrian crisis.

Effect of Active Case Finding on Prevalence and Transmission of Pulmonary Tuberculosis in Dhaka Central Jail, Bangladesh

BackgroundUnderstanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting.MethodsThe study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU).ResultsA total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as ‘modern’ and 100 (30%) strains as ‘ancestral’. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%.ConclusionsImplementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh.

Default Time from Tuberculosis Treatment in the Southern Republic of Benin Using Mixture Cure Model for Survival Analysis

Background: To date, this is the first statistical analysis of default time from tuberculosis (TB) treatment conducted in the republic of Benin. This cohort study assessed the cured fraction, the conditional probability of default (CPD) from treatment course and identified the risk factors predicting its timing. Methods: TB case was a patient with positive culture for the Mycobacterium tuberculosis complex or with two sputum smears positive for acid-fast bacilli. The 2008’s cohort of TB patients was extracted from Benin national TB registry. Active TB Patients who were diagnosed between November 2007 and December 2008 were included and followed up to December, 23 rd 2009 relative to their specific initiation date. Default was defined using the WHO guidelines. Primary endpoint was the time to default from the anti-TB treatment course. Risk factors were assessed with univariate and multivariate Cox regression integrating the mixture cure models. Results: More than 5% (n=64) of defaulters were identified with a cured fraction of 94.1%. About 3% of patients defaulted within the first 2 months (CPD = 0.025 ± 0.004). HIV/AIDS co-infection and TB history were independently associated with default time (log-rank = 35.21; P < 0.0001 and log-rank = 10.11; P = 0.0015 respectively). With Cox proportional hazards (PH) analysis, predictors of default time were HIV/AIDS, TB history and Age (hazard ratio [HR] = 3.82 [2.28; 6.41], P < 0.0001 for HIV-positive, HR = 0.13 [0.03; 0.53], P = 0.0045 for previous-TB infection and Age (HR = 3.49 [1.25; 9.74], P = 0.0170 for 65 years old or more, respectively). With logistic Cox PH mixture cure model HIV/AIDS and Age significantly increased the probability of default (Odds Ratios [OR] = 4.04 [2.64; 7.08], P < 0.0001 for HIV-positive, and OR = 4.23 [1.58; 12.10], P = 0.006 for 65 years old or more, respectively) whereas TB history significantly reduced default probability (OR = 0.04 [0.004; 0.54], P = 0.0148 for previous-TB infection. Conclusion: Whatever the alternative model considered, this study provides the first evidence that HIV/AID, TB history and Age were the major predictive factors of default time from anti-TB treatment in Benin. Therefore, additional efforts to improve the compliance of patients with anti-TB treatment through a better management of the co-infection with HIV/AIDS in accordance with patient’s specific age group may be an important feature of a prospective TB control strategy in the future. This should be emphasized in the early treatment course for these subgroups of TB patients.

Tuberculosis control strategies to reach the 2035 global targets in China: the role of changing demographics and reactivation disease.

BackgroundIn the last 20 years, China ramped up a DOTS (directly observed treatment, short-course)-based tuberculosis (TB) control program with 80% population coverage, achieving the 2015 Millennium Development Goal of a 50% reduction in TB prevalence and mortality. Recently, the World Health Organization developed the End TB Strategy, with an overall goal of a 90% reduction in TB incidence and a 95% reduction in TB deaths from 2015–2035. As the TB burden shifts to older individuals and China’s overall population ages, it is unclear if maintaining the current DOTS strategy will be sufficient for China to reach the global targets.MethodsWe developed an individual-based computational model of TB transmission, implementing realistic age demographics and fitting to country-level data of age-dependent prevalence over time. We explored the trajectory of TB burden if the DOTS strategy is maintained or if new interventions are introduced using currently available and soon-to-be-available tools. These interventions include increasing population coverage of DOTS, reducing time to treatment, increasing treatment success, and active case finding among elders > 65 years old. We also considered preventative therapy in latently infected elders, a strategy limited by resource constraints and the risk of adverse events.ResultsMaintenance of the DOTS strategy reduces TB incidence and mortality by 42% (95% credible interval, 27-59%) and 41% (5-64%), respectively, between 2015 and 2035. A combination of all feasible interventions nears the 2035 mortality target, reducing TB incidence and mortality by 59% (50-76%) and 83% (73-94%). Addition of preventative therapy for elders would enable China to nearly reach both the incidence and mortality targets, reducing incidence and mortality by 84% (78-93%) and 92% (86-98%).ConclusionsThe current decline in incidence is driven by two factors: maintaining a low level of new infections in young individuals and the aging out of older latently infected individuals who contribute incidence due to reactivation disease. While further reducing the level of new infections has a modest effect on burden, interventions that limit reactivation have a greater impact on TB burden. Tools that make preventative therapy more feasible on a large scale and in elders will help China achieve the global targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0341-4) contains supplementary material, which is available to authorized users.

Transmission of Mycobacterium tuberculosis in China: a population-based molecular epidemiologic study.

Understanding the transmission of Mycobacterium tuberculosis is essential for the development of efficient tuberculosis control strategies. China has the second-largest tuberculosis burden in the world. Recent transmission and infection with M. tuberculosis, particularly drug-resistant strains, may account for many new tuberculosis cases. We performed a population-based molecular epidemiologic study of pulmonary tuberculosis in China during 1 July 2009 to 30 June 2012. We defined clusters as cases with identical variable number tandem repeat genotype patterns and identified the risk factors associated with clustering, by logistic regression. Relative transmission rates were estimated by the sputum smear status and drug susceptibility status of tuberculosis patients. Among 2274 culture-positive tuberculosis patients with genotyped isolates, there were 705 (31.0%) tuberculosis patients in 287 clusters. Multidrug-resistant (MDR) tuberculosis (adjusted odds ratio [aOR], 1.86; 95% confidence interval [CI], 1.25-2.63) and infection with a Beijing family strain (aOR, 1.56; 95% CI, 1.23-2.96) were associated with clustering. Eighty-four of 280 (30.0%) clusters had a putative source case that was sputum smear negative, and 30.6% of their secondary cases were attributed to transmission by sputum smear-negative patients. The relative transmission rate for sputum smear negative compared with sputum smear-positive patients was 0.89 (95% CI, .68-1.10), and was 1.51 (95% CI, 1.00-2.24) for MDR tuberculosis vs drug-susceptible tuberculosis. Recent transmission of M. tuberculosis, including MDR strains, contributes substantially to tuberculosis disease in China. Sputum smear-negative cases were responsible for at least 30% of the secondary cases. Interventions to reduce the transmission of M. tuberculosis should be implemented in China.