A comparative impact evaluation of two human resource models for community-based active tuberculosis case finding in Ho Chi Minh City, Viet Nam

Background: To achieve the WHO End TB Strategy targets, it is necessary to detect and treat more people with active TB early. Scale–up of active case finding (ACF) may be one strategy to achieve that goal. Given human resource constraints in the health systems of most high TB burden countries, volunteer community health workers (CHW) have been widely used to economically scale up TB ACF. However, more evidence is needed on the most cost-effective compensation models for these CHWs and their potential impact on case finding to inform optimal scale-up policies. Methods: We conducted a two-year, controlled intervention study in 12 districts of Ho Chi Minh City, Viet Nam. We engaged CHWs as salaried employees (3 districts) or incentivized volunteers (3 districts) to conduct ACF among contacts of people with TB and urban priority groups. Eligible persons were asked to attend health services for radiographic screening and rapid molecular diagnosis or smear microscopy. Individuals diagnosed with TB were linked to appropriate care. Six districts providing routine NTP care served as control area. We evaluated additional cases notified and conducted comparative interrupted time series (ITS) analyses to assess the impact of ACF by human resource model on TB case notifications. Results: We verbally screened 321,020 persons in the community, of whom 70,439 were eligible for testing and 1138 of them started TB treatment. ACF activities resulted in a + 15.9% [95% CI: + 15.0%, + 16.7%] rise in All Forms TB notifications in the intervention areas compared to control areas. The ITS analyses detected significant positive post-intervention trend differences in All Forms TB notification rates between the intervention and control areas (p = 0.001), as well as between the employee and volunteer human resource models (p = 0.021). Conclusions: Both salaried and volunteer CHW human resource models demonstrated additionality in case notifications compared to routine case finding by the government TB program. The salaried employee CHW model achieved a greater impact on notifications and should be prioritized for scale-up, given sufficient resources

Seasonality in extra-pulmonary tuberculosis notifications in Germany 2004-2014- a time series analysis

Background Seasonality in tuberculosis (TB) has been found in different parts of the world, showing a peak in spring/summer and a trough in autumn/winter. The evidence is less clear which factors drive seasonality. It was our aim to identify and evaluate seasonality in the notifications of TB in Germany, additionally investigating the possible variance of seasonality by disease site, sex and age group. Methods We conducted an integer-valued time series analysis using national surveillance data. We analysed the reported monthly numbers of started treatments between 2004 and 2014 for all notified TB cases and stratified by disease site, sex and age group. Results We detected seasonality in the extra-pulmonary TB cases (N = 11,219), with peaks in late spring/summer and troughs in fall/winter. For all TB notifications together (N = 51,090) and for pulmonary TB only (N = 39,714) we did not find a distinct seasonality. Additional stratified analyses did not reveal any clear differences between age groups, the sexes, or between active and passive case finding. Conclusion We found seasonality in extra-pulmonary TB only, indicating that seasonality of disease onset might be specific to the disease site. This could point towards differences in disease progression between the different clinical disease manifestations. Sex appears not to be an important driver of seasonality, whereas the role of age remains unclear as this could not be sufficiently investigated.Peer Reviewe

Finding gaps in routine TB surveillance activities in Bangladesh.

BACKGROUND: TB was the leading cause of death from a single infectious pathogen globally between 2014 and 2019. Fine-scale estimates of TB prevalence and case notifications can be combined to guide priority-setting for strengthening routine surveillance activities in high-burden countries. We produce policy-relevant estimates of the TB epidemic at the second administrative unit in Bangladesh.METHODS: We used a Bayesian spatial framework and the cross-sectional National TB Prevalence Survey from 2015-2016 in Bangladesh to estimate prevalence by district. We used case notifications to calculate prevalence-to-notification ratio, a key metric of under-diagnosis and under-reporting.RESULTS: TB prevalence rates were highest in the north-eastern districts and ranged from 160 cases per 100,000 (95% uncertainty interval [UI] 80-310) in Jashore to 840 (UI 690-1020) in Sunamganj. Despite moderate prevalence rates, the Rajshahi and Dhaka Divisions presented the highest prevalence-to-notification ratios due to low case notifications. Resolving subnational disparities in case detection could lead to 26,500 additional TB cases (UI 8,500-79,400) notified every year. CONCLUSION: This study is the first to produce and map subnational estimates of TB prevalence and prevalence-to-notification ratios, which are essential to target prevention and treatment efforts in high-burden settings. Reaching TB cases currently missing from care will be key to ending the TB epidemic

Trends of Zambia’s tuberculosis burden over the past two decades

Objectives:  To study trends in Zambia’s TB notification rates between 1990 and 2010 and to ascertain progress made towards TB control. Methods:  Retrospective review of TB notification returns and TB programme reports for the period from 1990 to 2010. Results:  Two distinct TB trend periods were identified: a period of rising trends up to a peak between 1990 and 2004 and a period of moderately declining trends between 2004 and 2010. Treatment outcomes improved over the two decades. Data on trends in paediatric TB, TB in prisoners and TB in pregnant women remain scanty and unreliable owing to poor diagnostic capability. There were no data available on trends on drug-resistant TB because of the lack of laboratory services to perform drug sensitivity testing. Conclusions:  The period of increasing TB between 1990 and 2000 coincided with an increase in HIV/AIDS. The period of slightly decreasing TB between 2004 and 2010 can be attributed to improved TB care, sustained DOTS implementation and improvement in TB diagnostic services. Newer diagnostics technologies for the rapid diagnosis of active TB cases and for drug-resistant testing, recently endorsed by the WHO, need to be implemented into the national TB programmes to detect more cases and to provide epidemiological and surveillance data from which to obtain an evidence base for guided investments for TB control. Alignment of TB and HIV services is required to achieve improved management outcomes

Epidemiology and disease burden of tuberculosis in children: a global perspective

Our understanding of the tuberculosis (TB) epidemic in children is incomplete due to challenges in diagnosis and reporting. Children have also been largely excluded from research and advocacy. However, the tide appears to be turning and interest in pediatric TB is increasing. In this article, we explore the epidemiology of childhood TB by first reviewing the natural history of TB in children and the factors that impact on each of the stages from exposure to disease. We then discuss how these factors affect what we see at a country and regional level. Finally, we assess the burden of childhood TB globally. © 2014 Seddon and Shingadia

Investigating the impact of TB case-detection strategies and the consequences of false positive diagnosis through mathematical modelling.

BACKGROUND: Increasing case notifications is one of the top programmatic priorities of National TB Control Programmes (NTPs). To find more cases, NTPs often need to consider expanding TB case-detection activities to populations with increasingly low prevalence of disease. Together with low-specificity diagnostic algorithms, these strategies can lead to an increasingly high number of false positive diagnoses, which has important adverse consequences. METHODS: We apply TIME, a widely-used country-level model, to quantify the expected impact of different case-finding strategies under two scenarios. In the first scenario, we compare the impact of implementing two different diagnostic algorithms (higher sensitivity only versus higher sensitivity and specificity) to reach programmatic screening targets. In the second scenario, we examine the impact of expanding coverage to a population with a lower prevalence of disease. Finally, we explore the implications of modelling without taking into consideration the screening of healthy individuals. Outcomes considered were changes in notifications, the ratio of additional false positive to true positive diagnoses, the positive predictive value (PPV), and incidence. RESULTS: In scenario 1, algorithm A of prolonged cough and GeneXpert yielded fewer additional notifications compared to algorithm B of any symptom and smear microscopy (n = 4.0 K vs 13.8 K), relative to baseline between 2017 and 2025. However, algorithm A resulted in an increase in PPV, averting 2.4 K false positive notifications thus resulting in a more efficient impact on incidence. Scenario 2 demonstrated an absolute decrease of 11% in the PPV as intensified case finding activities expanded into low-prevalence populations without improving diagnostic accuracy, yielding an additional 23 K false positive diagnoses for an additional 1.3 K true positive diagnoses between 2017 and 2025. Modelling the second scenario without taking into account screening amongst healthy individuals overestimated the impact on cases averted by a factor of 6. CONCLUSION: Our findings show that total notifications can be a misleading indicator for TB programme performance, and should be interpreted carefully. When evaluating potential case-finding strategies, NTPs should consider the specificity of diagnostic algorithms and the risk of increasing false-positive diagnoses. Similarly, modelling the impact of case-finding strategies without taking into account potential adverse consequences can overestimate impact and lead to poor strategic decision-making

Exploring the effects of BCG vaccination in patients diagnosed with tuberculosis: Observational study using the Enhanced Tuberculosis Surveillance system.

BACKGROUND: Bacillus Calmette-Guérin (BCG) is one of the most widely-used vaccines worldwide. BCG primarily reduces the progression from infection to disease, however there is evidence that BCG may provide additional benefits. We aimed to investigate whether there is evidence in routinely-collected surveillance data that BCG vaccination impacts outcomes for tuberculosis (TB) cases in England. METHODS: We obtained all TB notifications for 2009-2015 in England from the Enhanced Tuberculosis surveillance system. We considered five outcomes: All-cause mortality, death due to TB (in those who died), recurrent TB, pulmonary disease, and sputum smear status. We used logistic regression, with complete case analysis, to investigate each outcome with BCG vaccination, years since vaccination and age at vaccination, adjusting for potential confounders. All analyses were repeated using multiply imputed data. RESULTS: We found evidence of an association between BCG vaccination and reduced all-cause mortality (aOR:0.76 (95%CI 0.64-0.89), P:0.001) and weak evidence of an association with reduced recurrent TB (aOR:0.90 (95%CI 0.81-1.00), P:0.056). Analyses using multiple imputation suggested that the benefits of vaccination for all-cause mortality were reduced after 10 years. CONCLUSIONS: We found that BCG vaccination was associated with reduced all-cause mortality in people with TB although this benefit was less pronounced more than 10 years after vaccination. There was weak evidence of an association with reduced recurrent TB

Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

Aspectos epidemiológicos da tuberculose em uma região do estado de São Paulo

Orientadora: Profa. Dra. Astrid Wiens SouzaCoorientador: Prof. Dr. Bruno Salgado RiverosDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Assistência Farmacêutica. Defesa : Curitiba, 24/02/2022Inclui referênciasResumo: A tuberculose (TB) é uma doença infectocontagiosa de notificação obrigatória no Brasil. O objetivo desse estudo foi analisar a incidência, perfil epidemiológico e a completude das notificações dos casos de TB registrados numa região do Estado de São Paulo em um período de 10 anos e avaliar o impacto da pandemia da COVID-19 nas notificações. Trata-se de um estudo retrospectivo, de metodologia mista, parte transversal e parte longitudinal, de análise de notificações de pacientes adultos diagnosticados com TB. Os dados de janeiro de 2010 a dezembro de 2020 foram extraídos do sistema TBweb. Variáveis sociodemográficas (sexo, raça e escolaridade), clínicas (forma clínica, tipos de casos e comorbidades) e acompanhamento do tratamento (tipo e tratamento, taxa de cura, internação, taxa de abandono e óbito) foram coletados e analisados. A completude das notificações de TB e o impacto da pandemia na qualidade, perfil e completude das notificações de TB foi avaliado considerando o ano de 2020. Análises estatísticas descritivas e exploratórias foram conduzidas. Os resultados foram reportados de acordo com a ferramenta Strengthening the Reporting of Observational Studies in Epidemiology - STROBE para estudos observacionais. Foram incluídas 1509 notificações de pacientes com TB. A idade mediana foi de 49 anos, com predomínio do sexo masculino (71%), raça branca (42%) e 4 a 11 anos de escolaridade (49,3%). A forma pulmonar foi encontrada em 85% das notificações e em 70% dos casos foi realizada a baciloscopia do escarro para diagnóstico de TB. Na avaliação do impacto da pandemia nas notificações, em 2020 foi verificada uma queda de 36% na incidência no número de notificações de TB com ênfase entre julho e agosto de 2020, mesmo período em que ocorreu o auge dos casos de COVID-19 na região. Não houve diferença na completude das notificações em 2020, comparado aos anos anteriores. O tratamento supervisionado ocorreu em apenas 30 % dos casos, houve 14% de abandono do tratamento e 70% de cura no encerramento do caso. Essas evidências podem orientar gestores e profissionais de saúde nas decisões de prestação de cuidados e destacam a necessidade de esforços adicionais na vigilância e controle da TB, durante e após a pandemia. de esforços adicionais na vigilância e controle da TB, durante e após a pandemia.Abstract: Tuberculosis (TB) is a notifiable infectious disease in Brazil. The aim of this study was to analyze the incidence, epidemiological profile and completeness of notifications of TB cases registered in a region of the State of São Paulo over a period of 10 years and to assess the impact of the COVID-19 pandemic on notifications. This is a retrospective study, with a mixed methodology, part cross-sectional and part longitudinal, of analysis of notifications of adult patients diagnosed with TB. Data from January 2010 to December 2020 were extracted from the TBWeb system. Sociodemographic variables (gender, race and education), clinical variables (clinical form, types of cases and comorbidities) and follow-up of treatment (type and treatment, cure rate, hospitalization, dropout rate and death) were collected and analyzed. The completeness of TB notifications and the impact of the pandemic on the quality, profile and completeness of TB notifications were evaluated considering the year 2020. Descriptive and exploratory statistical analyzes were conducted. The results were reported according to the Strengthening the Reporting of Observational Studies in Epidemiology - STROBE tool for observational studies. 1,509 notifications of patients with TB were included. The median age was 49 years, with a predominance of males (71%), white race (42%) and 4 to 11 years of schooling (49.3%). The pulmonary form was found in 85% of the reports and in 70% of the cases sputum smear microscopy was performed for the diagnosis of TB. In assessing the impact of the pandemic on notifications, in 2020 there was a 36% decrease in the incidence in the number of TB notifications, with emphasis on between July and August 2020, the same period in which the peak of COVID-19 cases in the region occurred. There was no difference in the completeness of notifications in 2020 compared to previous years. Supervised treatment occurred in only 30% of the cases, there was 14% dropout of treatment and 70% cure at case closure. This evidence can guide managers and health professionals in care delivery decisions and highlights the need for additional efforts in TB surveillance and control, during and after the pandemic

Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV.

BACKGROUND: In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions. DISCUSSION: District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART. SUMMARY: Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not