Tuberculosis Epidemic Research Articles

TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages

Mycobacterium tuberculosis (Mtb) strains are classified into different phylogenetic lineages (L), three of which (L2/L3/L4) emerged from a common progenitor after the loss of the MmpS6/MmpL6-encoding Mtb-specific deletion 1 region (TbD1). These TbD1-deleted “modern” lineages are responsible for globally-spread tuberculosis epidemics, whereas TbD1-intact “ancestral” lineages tend to be restricted to specific geographical areas, such as South India and South East Asia (L1) or East Africa (L7). By constructing and characterizing a panel of recombinant TbD1-knock-in and knock-out strains and comparison with clinical isolates, here we show that deletion of TbD1 confers to Mtb a significant increase in resistance to oxidative stress and hypoxia, which correlates with enhanced virulence in selected cellular, guinea pig and C3HeB/FeJ mouse infection models, the latter two mirroring in part the development of hypoxic granulomas in human disease progression. Our results suggest that loss of TbD1 at the origin of the L2/L3/L4 Mtb lineages was a key driver for their global epidemic spread and outstanding evolutionary success.

Spatial Analysis of Childhood Tuberculosis and Social Determinants in Bandar Lampung

Childhood tuberculosis is an overlooked aspect of the current tuberculosis epidemics; even the incidence is increasing and may influence children's growth and development. Several researches have studied social determinants as TB risk factors, but only a few researches have studied spatial analysis of childhood tuberculosis and social determinants. This research aimed to study spatial analysis of childhood TB and social determinants in Bandar Lampung, Indonesia. This research was cross sectional study which involved five community health centers that have childhood TB cases. Population of this research was all childhood tuberculosis cases in the study site. Sample of this research was 73 cases. Variables of this research were samples’ residence geographical coordinates and social determinants (population density and proportion of poor family) of the related sub districts. Data was collected through CHSs’ and sub districts’ secondary data which then analyzed using overlay spatial analysis. The results showed that childhood TB tend to group in middle to high population density and middle proportion of poor families areas. Therefore, regarding in reducing childhood TB incidence, TB control programs should elaborate social determinants actions in areas with low social determinants.

Incidence of Tuberculosis as a Opportunistic Infection in Patients with HIV Getting Combined Anti Retroviral Therapy

Introduction: The risk of active Tuberculosis increases after HIV seroconversion. It progressively increases with declining immunity. Tuberculosis (TB) epidemics in HIV has led to a dramatic upsurge in global TB incidence, resulting in remarkable increase in morbidity and mortality. Many clinical studies had shown that TB is one of the commonest opportunistic infection. This study is conducted to see the incidence of tuberculosis as an opportunistic infection in patients with HIV getting combined antiretroviral therapy (cART)
 Materials and Methods: This was a hospital based cross-sectional comparative study. Five hundred patients with HIV who are getting cART were enrolled in the study.
 Results: Analysis of individuals with HIV in our study amongst the 500 patients 266 (53.2%) were males and the remaining 234 (46.68%) were females. Amongst these HIV patients 48(18.04%) males and 17(7.26%) females had tuberculosis. 65(13%) of patients were TB/HIV co-infected. 2(4.1%) of these male TB/HIV patients had cervical gland TB.
 Conclusion: The incidence of tuberculosis in HIV infected individuals is high. TB is the commonest opportunistic infection (OIs) in people living with HIV/AIDS. Males are predominant gender to have TB/HIV co-infection.

Treatment Outcome of Tuberculosis and Associated Factors among TB-HIV Co-Infected Patients at Public Hospitals of Harar Town, Eastern Ethiopia. A five-year retrospective study

BackgroundThe bidirectional relationship between the twin epidemics of Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) causes major global health challenges in the twenty-first century. TB-HIV co-infected people are facing multifaceted problems like high lost to follow up rates, poor treatment adherence, high TB recurrence rate, and high mortality risk. Our objective was to assess the outcomes of TB treatment and associated factors among TB-HIV co-infected patients in Harar town, Eastern part of Ethiopia, 2018.MethodsA retrospective study was conducted among systematically selected 349 TB/HIV co-infected patients who registered from 2012 to 2017 in two public hospitals in Harar town. The data were collected through document review by using a pre-tested structured data extraction checklist. The data were analyzed using SPSS Version 21. Bivariate and multivariate logistic regression were determined at 95% confidence intervals.ResultsAmong the 349 TB/HIV co-infected patients included in the study, 30.1% were cured, 56.7% had completed their treatment, 7.7% died, 1.7% were lost to follow up, and 3.7% were treatment failure. Overall, 86.8% of the TB-HIV co-infected patients had successful TB treatment outcomes. The patients who were on re-treatment category (AOR = 2.91, 95% CI: 1.17–7.28), who had a history of opportunistic infection (AOR = 3.68, 95% CI: 1.62–8.33), and who did not take co-trimoxazole prophylaxis (AOR = 3.54, 95% CI: 1.59–7.89) had 2.91, 3.68, and 3.54 times higher odds of having unsuccessful TB treatment outcome than their counterparties, respectively. The chance of unsuccessful TB treatment outcome was 4.46 (95% CI: 1.24–16.02), 5.94 (95% CI: 1.87–18.85), and 3.01 (95% CI: 1.15–7.91) times higher among TB/HIV patients in stage 2, 3 and 4 than those in stage 1, respectively.ConclusionsThe overall rate of the success of the TB treatment among TB-HIV co-infected patients in this study was higher compared with many previous studies. TB/HIV patients with a history of previous TB treatment, smear-positive pulmonary TB, late HIV stage, history of opportunistic infection and not being on co-trimoxazole prophylaxis therapy were at a high risk of getting poor treatment outcomes.

Lessons from the field: Gender roles and researcher reflexivity in smoking cessation in South Asia

Abstract Background In South Asia, dual epidemics of smoking and tuberculosis (TB) have contributed to a high burden of lung disease. To address these health risks, the TB & Tobacco study uses the TB diagnosis as a teachable moment and implements a behaviour support counselling intervention, conducted by TB health workers, for patients in Bangladesh, Nepal and Pakistan. In this region, smoking tobacco is perceived as problematic for women, and being confronted with questions on smoking from a health professional may be uncomfortable for men and women. Anticipating these challenges, we incorporated gender sensitivity into training of health workers. Methods During implementation of the cessation support in routine TB care, a process evaluation assessed interactions between participants and the intervention through interviews with health workers and patients with TB participating in the cessation program. This presentation focusses on a retrospective self-reflection on how we conceptualized gender roles based on prior research, and how research findings partially challenged these assumptions. Findings While parts of our interview findings point towards smoking as a stigmatized practice for women and some men in South Asia as expected, several male and female respondents across socio-economic and geographical spheres contradicted this assumption. We discovered that health workers’ self-efficacy and perceived smoking stigma among health workers influenced whether they discussed smoking with women or minors. Many patients, on the other hand, told us that they were interested in receiving help to cure their TB and were willing to talk to about smoking with their health workers and their family members. Conclusions Patients in this study were more open to talking about smoking than anticipated. When including gender sensitivity into the standard training for health workers, we should be careful not to increase doubts in health workers about addressing smoking with women.

Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa

Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal ∼400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.

MicroRNA Mediated Changes in Drug Metabolism and Target Gene Expression by Efavirenz and Rifampicin In Vitro: Clinical Implications.

Efavirenz (EFV) and rifampicin (RMP) are widely prescribed in Africa for treatment of HIV/AIDS and tuberculosis epidemics. Exposure to medicines can alter drug metabolism, for example, through changes in expression of microRNAs. We report, in this study, novel observations on the ways in which EFV and RMP change microRNA expression signatures in vitro in HepaRG cells. Additionally, we discuss the clinical implications of changes in expression of drug-metabolizing enzyme genes, such as CYP3A4, CYP3A5, UGT1A1, CYP2B6, and NR1I3. Differentiated HepaRG cells were treated with EFV (6.4 μM) or RMP (24.4 μM) for 24 h. Treatment of HepaRG cells with EFV resulted in a significant increase in messenger RNA (mRNA) expression for CYP3A4 (12.51-fold, p = 0.002), CYP3A5 (2.10-fold, p = 0.019), and UGT1A1 (2.52-fold, p = 0.005), whereas NR1I3 expression decreased (0.41-fold, p = 0.02). On the other hand, treatment of HepaRG cells with RMP resulted in a significant increase in mRNA expression for CYP2B6 (6.68-fold, p = 0.007) and CYP3A4 (111.96-fold, p = 0.001), whereas NR1I3 expression decreased (0.46-fold, p = 0.033). These data point to several important clinical implications through changes in drug/drug interaction risks and achieving optimal therapeutics. All in all, this study shows that differential expression of microRNAs after treatment with EFV and RMP adds another layer of complexity that should be incorporated in pharmacogenomic algorithms to render drug response more predictable.

Cloning and characterization of Rv1980c gene encoding MPT64 Protein from Mycobacterium tuberculosis as a new candidate vaccine of tuberculosis

Pathogenic mycobacteria are one of the major causes of human mortality in the word. Mycobacterium tuberculosis is an etiological agent of human tuberculosis. Designing new vaccines including recombinant protein vaccines may be considered as a new approach for preventing or reducing tuberculosis epidemics. In order to construct protein recombinant as candidate vaccine, the Rv1980c gene encoding MPT64 protein was amplified from M. tuberculosis H37Rv strain genomic DNA using the PCR method and inserted into the cloning vector pGEM-T Easy. The recombinant plasmid pGEM-T Easy-MPT64 was then transformed into E. coli JM109 and cultivated under standard procedure, followed by plasmid extraction, PCR amplification, and DNA sequencing. The correct Rv1980c gene was confirmed by DNA sequencing and subcloned into expression vector pQE30Xa to yield recombinant plasmid pQE30Xa-MPT64, and transformed into E. coli BL21 strain. Transformed white recombinant colony was selected, cultured, induced with 40 μM IPTG, and identified using SDS-PAGE electrophoresis method. The molecular weight was found to be about 24 kDa and identified as recombinant protein MPT64. The target gene has been cloned into host E. coli BL-21 strain and expressed successfully as a soluble protein. The recombinant fusion recombinant protein MPT64 paves the way for tuberculosis diagnosis and vaccine development in the future, especially in Indonesia.

Bench, bed and beyond: Communication and responsibility in decentralised tuberculosis care.

BackgroundSouth Africa faces one of the world’s worst drug-resistant tuberculosis epidemics. Implementing successful care in this context has proven challenging for a number of reasons. Communication is an essential yet neglected feature of care and research in the field of tuberculosis.AimThe primary aim of this qualitative study was to explore communication facilitators and barriers at several tuberculosis care sites. In this article, we focus on communication practices across the chain of diagnosis, treatment, discharge and follow-up in decentralised care approaches and present evidence of gaps in communication.SettingThe study was conducted at three tuberculosis care sites in two South African provinces.MethodsParticipants included healthcare workers, patients, community members and home-based carers. Data included 79 interviews, 4 video-recorded interactions between patients and healthcare workers, and ethnographic observations at each site. We analysed the data using thematic analysis and a qualitative sociolinguistic framework.ResultsCommunication in decentralised care contexts is complex because of multiple sites and role players. Responsibility for communication seems to be unduly placed on patients, treatment guidelines are not implemented consistently across sites and assumptions are made about the role of others in the chain. Patient and healthcare worker reports suggest confusion and frustration.ConclusionCommunication in the South African tuberculosis care context appears fragile and current mechanisms for detecting flaws in the care chain are not sensitive to communication issues. We make recommendations for strengthening home-based care resources, providing team training and focusing on communication processes in monitoring and evaluating systems.

High incidence of drug-resistant Mycobacterium tuberculosis in Hainan Island, China.

To assess the proportion of drug-resistant tuberculosis (TB) cases and to identify independent risk factors associated with drug-resistant TB in Hainan. Descriptive analysis of demographic and clinical data of culture-positive TB patients to assess the trends in drug-resistant TB at the Provincial Clinical Center on Tuberculosis of Hainan between 2014 and 2017. 994 patients were recruited into the study. Overall, the proportion of patients resistant to at least one TB drug tested was 36.1% (359/994). The most frequent resistance was to isoniazid (INH, 29.8%), followed by rifampin (RIF, 29.3%), streptomycin (19.3%), ofloxacin (OFX, 17.4%), ethambutol (9.5%) and kanamycin (KAN, 3.2%). Of 291 RIF-resistant isolates, 228 (78.4%) were also resistant to INH, while the remaining 63 (21.6%) were susceptible to INH. Among those with multidrug-resistant tuberculosis (MDR-TB), 41.2% had additional resistance to OFX and 3.9% to KAN. 8.8% of MDR-TB patients were affected by extensively drug-resistant (XDR-TB). Females were more likely to infected with MDR-TB than males, and young people (<20years old) were more likely to have MDR-TB; patients exhibited decreasing MDR-TB risk with increasing age. Our data provide the first primary understanding of the drug-resistant TB epidemic in Hainan. The high incidence of drug resistance, especially RIF and FQ resistance, highlight the importance of interventions for preventing epidemics of drug-resistant TB. Younger age is an independent predictor of MDR-TB, reflecting the potential transmission in this population.

THE HIV AND TUBERCULOSIS TENDENCY IN PENITENTIARY SYSTEM OF NORTH-WEST REGION OF RUSSIA

The penitentiary system is one of the leading factors in preservation and the spread of HIV infection and tuberculosis epidemics among the general population. The aim of the analytical review is to assess the trends of the HIV and tuberculosis epidemics, as monoinfections in prisons, and to evaluate their influence on the general situation in the North-West Region. In the study were used data from the Rosstat and the Ministry of Justice annual reporting forms during 2007–2017. Results. Tuberculosis incidence, prevalence and mortality in the North-West Region penitentiary system for the review period have significantly reduced, the HIV incidence and mortality rates also tend to go down, nevertheless the HIV prevalence is continuing to go up. At the same time, in either case, there is a significant excess of indicators in correctional system over similar data among the general population. Conclusion. In the North-West Region the tuberculosis situation in the penitentiary facilities is improving, the HIV situation is remaining problematic. The correctional system of the Arkhangelsk oblast, the Republics of Karelia and Komi and the Novgorod oblast have a greatest impact on the tuberculosis and HIV epidemic situation among the general population, the least influence is in the Kaliningrad oblast.

Pulmonary tuberculosis with atypical presentation because of unknown previous HIV infection – case report

Abstract Background People coinfected with tuberculosis (TB) and human immunodeficiency virus (HIV) are 20–37 times more likely to develop active TB disease than non-HIV-infected people. Syndemic interaction between HIV and TB epidemics has made testing for TB a must for HIV-infected people and vice versa. We present the case of a young male diagnosed with HIV infection, due to mandatory HIV testing for all TB cases in Romania. Case presentation A 30-year-old man was hospitalized for fever, chills and productive cough not influenced by previous antibiotic home treatment. He was admitted with tachycardia and bilateral presence of coarse crackles in lower pulmonary areas. Chest X-ray suggested bilateral bronchopneumonia; the results from blood tests showed inflammation, leukocytosis and anaemia. Hemocultures were negative. Under wide-spectrum antibiotic treatment, his general condition partially improved, but on the seventh day, chest X-ray revealed abscess in the left inferior lobe and the progression of previous lesions. Chest computed tomography revealed multiple large consolidation areas in both lung areas, a 13 cm diameter abscess and multiple mediastinal adenopathy of 2–4 cm in diameter. Acid fast bacilli smear from sputum was positive. After the diagnosis of pulmonary TB, anti-TB treatment was started; the patient was subsequently diagnosed with HIV infection. He received specific anti-TB treatment, and 3 weeks later, retroviral treatment was initiated. Clinical evolution was favourable and radiological appearance improved. In addition, he did not present any adverse effects of therapy. Conclusions HIV testing for all TB cases is a must because HIV-TB coinfection raises important diagnostic and treatment problems.

The phytochemical bergenin as an adjunct immunotherapy for tuberculosis in mice

The widespread availability and use of modern synthetic therapeutic agents have led to a massive decline in ethnomedical therapies. However, these synthetic agents often possess toxicity leading to various adverse effects. For instance, anti-tubercular treatment (ATT) is toxic, lengthy, and severely impairs host immunity, resulting in posttreatment vulnerability to reinfection and reactivation of tuberculosis (TB). Incomplete ATT enhances the risk for the generation of multidrug- or extensively drug-resistant (MDR or XDR, respectively) variants of Mycobacterium tuberculosis (M. tb), the TB-causing microbe. Therefore, a new therapeutic approach that minimizes these risks is urgently needed to combat this deadly disease and prevent future TB epidemics. Previously, we have shown that the phytochemical bergenin induces T helper 1 (Th1)- and Th17 cell-based protective immune responses and potently inhibits mycobacterial growth in a murine model of M. tb infection, suggesting bergenin as a potential adjunct agent to TB therapy. Here, we combined ATT therapy with bergenin and found that this combination reduces immune impairment and the length of treatment in mice. We observed that co-treatment with the anti-TB drug isoniazid and bergenin produces additive effects and significantly reduces bacterial loads compared with isoniazid treatment alone. The bergenin co-treatment also reduced isoniazid-induced immune impairment; promoted long-lasting, antigen-specific central memory T cell responses; and acted as a self-propelled vaccine. Of note, bergenin treatment significantly reduced the bacterial burden of a multidrug-resistant TB strain. These observations suggest that bergenin is a potent immunomodulatory agent that could be further explored as a potential adjunct to TB therapy.

Spoligotyping analysis of Mycobacterium tuberculosis in Khyber Pakhtunkhwa area, Pakistan.

Background: Spoligotyping is a reproducible, reverse hybridization approach for genotyping of Mycobacterium tuberculosis complex (MTBC). Molecular typing of MTBC is helpful for understanding and controlling tuberculosis epidemics.Methods: Spoligotyping was performed on 166 clinical isolates of Mycobacterium tuberculosis (MTB) collected from 25 districts of Khyber Pakhtunkhwa, Pakistan. Results were compared to SITVIT2, an online database developed by the Institut Pasteur de la Guadeloupe, France.Results: Spoligotyping results showed that 145 strains (88%) displayed known patterns while 21 (12%) were new. Lineage 3/Central Asian strain (L3/CAS) was the predominant family (73%, χ2=19.9, P=0.001), followed by L2/Beijing (5.4%) and L4 (4.2%). L3/CAS1-Delhi was the major sublineage (82%) among the L3/CAS family (χ2=664, P=0.0001). Analysis showed that the majority of the clinical isolates with an unknown pattern had an evolutionary link with the L3/CAS strain, and nine (5.4%) of the unknown strains were epidemiologically linked and were tentatively named L3/CAS-KP (Khyber Pakhtunkhwa).Conclusion: The present study demonstrated that L3/CAS is the predominant lineage of MTB, widely distributed in different areas of the Khyber Pakhtunkhwa province of Pakistan. Spoligotyping patterns of some clinical isolates could not be matched to other reported patterns in an international database. Other tools, such as mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR), will be helpful in future investigations into the epidemiological characteristics of clinical isolates in the Khyber Pakhtunkhwa province.

Time-series analysis of geographically specific monthly number of newly registered cases of active tuberculosis in Japan.

BackgroundUnderstanding seasonality of tuberculosis (TB) epidemics may lead to identify potentially modifiable risk factors. Studies conducted outside Japan have found seasonal variation among reported TB cases, with peaks in spring and summer and low prevalence in fall and winter. One hypothesis regarding spring or summer peaks in TB epidemics is that TB transmission likely increases in winter because of indoor crowding and poor ventilation, with development of primary TB among socially vulnerable people in spring and summer. Another plausible explanation is that vitamin D deficiency in winter depresses immunity, increasing the TB reactivation risk in these seasons. Previous studies suggest latitude-dependent factors, including reduced winter sunlight and its effect on vitamin D levels. Here, we investigated mechanisms of seasonality in TB epidemics in Japan, according to the effects of crowding and latitude.MethodsWe used time-series analysis consisting of spectral analysis and least-squares method, to analyse geographically specific monthly number of newly registered cases of all forms of active TB in all 47 prefectures of Japan during 1998–2015.ResultsIn all power spectral densities for the 47 prefectures, spectral lines were observed at frequency positions corresponding to a 1-year cycle. The degree of this seasonality was associated with population density. We did not detect greater amplitude of seasonality at higher latitudes, suggesting that latitude-dependent factors, including reduced winter sunlight and its potential effect on vitamin D levels, do not contribute significantly to seasonality in Japan.Discussion and conclusionIn districts with high population density, measures are needed to address two specific types of active infection risk in adolescents and middle-aged adults: (i) public transport use, and (ii) irregular employment with no periodic medical examinations. To control active TB epidemics, investigating periodic structures in the temporal patterns of active TB in each district and each age group is important.

Global epidemiology of tuberculosis, a comparative study of the six WHO regions in 2018

Introduction: Tuberculosis (TB) remains a global emergency and is one of the major threats to human and public health, more than 60 years of its medical treatment, as well as the economic and social development of societies. More than 2 billion individuals are infected with mycobacterium, causing the morbidity and mortality of 10 and 2 million individuals, respectively. The current study was accomplished aiming to investigate the TB disease status and indicators of achieving the goal of ending the TB epidemics by 2035. Methods: This was a comparative study conducted in a library and the main source of information used included the reports published by the World Health Organization (WHO) and its regional organizations profile, the United Nations Development Program (UNDP), World Bank Group (WBG), and studies. Results: The highest incidence rate was in Africa and South-East Asia, with the lowest incidence in the Americas and Europe regions. In the Eastern Mediterranean region, the incidence of extrapulmonary TB (EPTB) was about 10% higher than in other areas. The highest success rate of TB treatment was in the Western Pacific region and the lowest in the United States and Europe. Conclusion: Over 1 billion US dollars have been spent in funding for the fight against TB. Health policymakers, especially in the Middle Eastern region, should pay particular attention to allocating national and local resources to this disease and rely less on international and humanitarian resources. In order to achieve the goal of ending the TB epidemic END-TB 2035, in addition to addressing the economic and social well-being of citizens, it is essential to focus on early detection and diagnosis of disease and effective treatment with strategy implementation [Directly Observed Treatment Short course (DOTS)].

Operationalization of bi-directional screening for tuberculosis and diabetes in private sector healthcare clinics in Karachi, Pakistan

BackgroundMany countries are facing overlapping epidemics of tuberculosis (TB) and diabetes mellitus (DM). Diabetes increases the overall risk of developing Tuberculosis (TB) and contributes to adverse treatment outcomes. Active screening for both diseases can reduce TB transmission and prevent the development of complications of DM. We investigated bi-directional TB-DM screening in Karachi, Pakistan, a country that ranks fifth among high TB burden countries, and has the seventh highest country burden for DM.MethodsBetween February to November 2014, community-based screeners identified presumptive TB and DM through verbal screening at private health clinics. Individuals with presumptive TB were referred for a chest X-ray and Xpert MTB/RIF. Presumptive DM cases had random blood glucose (RBS) tested. All individuals with bacteriologically positive TB were referred for diabetes testing (RBS). All pre-diabetics and diabetics were referred for a chest X-ray and Xpert MTB/RIF test. The primary outcomes of this study were uptake of TB and DM testing.ResultsA total of 450,385 individuals were screened, of whom 18,109 had presumptive DM and 90,137 had presumptive TB. 14,550 of these individuals were presumptive for both DM and TB. The uptake of DM testing among those with presumptive diabetes was 26.1% while the uptake of TB testing among presumptive TB cases was 5.9%. Despite efforts to promote bi-directional screening of TB and DM, the uptake of TB testing among pre-diabetes and diabetes cases was only 4.7%, while the uptake of DM testing among MTB positive cases was 21.8%.ConclusionWhile a high yield for TB was identified among pre-diabetics and diabetics along with a high yield of DM among individuals diagnosed with TB, there was a low uptake of TB testing amongst presumptive TB patients who were recorded as pre-diabetic or diabetic. Bi-directional screening for TB and DM which includes the integration of TB diagnostics, DM screening and TB-DM treatment within existing health care programs will need to address the operational challenges identified before implementing this as a strategy in public health programs.

HIV infection and unknown HIV status among tuberculosis patients in Ethiopia: a systematic review and meta-analysis

Each case of human immunodeficiency virus (HIV) infection worsens the global HIV situation, leads to the failure to achieve tuberculosis (TB) control targets worldwide, and impacts on the use of health service resources. We determined the prevalence of HIV infection among TB patients and the proportion of TB patients with unknown HIV status in Ethiopia. We searched PubMed, EMBASE, Google Scholar and Web of Science electronic databases. Heterogeneity of the included studies was checked using the I² statistic and publication bias was assessed using funnel plots and Egger's regression statistical test. We employed a random-effects model to determine the pooled prevalence of HIV infection and unknown HIV status. A sensitivity analysis was also conducted to examine the effect of possible outliers on the overall estimate. The prevalence of HIV infection among TB patients and the proportion of TB patients with unknown HIV status was respectively 23.4% (95%CI 19.6-27.2) and 6.4% (95%CI 1.7-11.0). Based on geographical location, the prevalence of HIV infection was 31.4% (95%CI 19.2-43.6) in Amhara Region, 23.2% (95%CI 9.9-36.5) in Oromia, 20.9% (95%CI 17.8-24.0) in Addis Ababa and 16.5% (95%CI 12.0-21.0) in Southern Nations, Nationalities and Peoples' Region (SNNPR). In Ethiopia, almost one in four TB patients is infected with HIV. Given the epidemiological variation of Ethiopia, responsive, integrated sustainable programmes for HIV and TB are essential to minimise the epidemics of HIV infection and TB.

Using behaviour change theory to train health workers on tobacco cessation support for tuberculosis patients: a mixed-methods study in Bangladesh, Nepal and Pakistan

BackgroundLow- and middle-income countries (LMICs) are disproportionately impacted by interacting epidemics of tuberculosis (TB) and tobacco consumption. Research indicates behavioural support delivered by health workers effectively promotes tobacco cessation. There is, however, a paucity of training to support LMIC health workers deliver effective tobacco cessation behavioural support. The TB and Tobacco Consortium undertook research in South Asia to understand factors affecting TB health workers’ delivery of tobacco cessation behavioural support, and subsequently developed a training package for LMICs.MethodsUsing the “capability, opportunity, and motivation as determinants of behaviour” (COM-B) framework to understand any issues facing health worker delivery of behaviour support, we analysed 25 semi-structured interviews and one focus group discussion with TB health workers, facility in-charges, and national tuberculosis control programme (NTP) staff members in each country. Results were integrated with findings of an adapted COM-B questionnaire on health worker confidence in tobacco cessation support delivery, administered to 36 TB health workers. Based on findings, we designed a guide and training programme on tobacco cessation support for health workers.ResultsQualitative results highlighted gaps in the majority of health workers’ knowledge on tobacco cessation and TB and tobacco interaction, inadequate training on patient communication, insufficient resources and staff support, and NTPs’ non-prioritization of tobacco cessation in all three countries. Questionnaire results reiterated the knowledge deficits and low confidence in patient communication. Participants suggested strengthening knowledge, skills, and competence through training and professional incentives. Based on findings, we developed an interactive two-day training and TB health worker guide adaptable for LMICs, focusing on evidence of best practice on TB and tobacco cessation support, communication, and rapport building with patients.ConclusionsTB health workers are essential in addressing the dual burden of TB and tobacco faced by many LMICs. Factors affecting their delivery of tobacco cessation support can be identified using the COM-B framework, and include issues such as individuals’ knowledge and skills, as well as structural barriers like professional support through monitoring and supervision. While structural changes are needed to tackle the latter, we have developed an adaptable and engaging health worker training package to address the former that can be delivered in routine TB care.Trial registrationISRCTN43811467.

Evaluating strategies for control of tuberculosis in prisons and prevention of spillover into communities: An observational and modeling study from Brazil.

BackgroundIt has been hypothesized that prisons serve as amplifiers of general tuberculosis (TB) epidemics, but there is a paucity of data on this phenomenon and the potential population-level effects of prison-focused interventions. This study (1) quantifies the TB risk for prisoners as they traverse incarceration and release, (2) mathematically models the impact of prison-based interventions on TB burden in the general population, and (3) generalizes this model to a wide range of epidemiological contexts.Methods and findingsWe obtained individual-level incarceration data for all inmates (n = 42,925) and all reported TB cases (n = 5,643) in the Brazilian state of Mato Grosso do Sul from 2007 through 2013. We matched individuals between prisoner and TB databases and estimated the incidence of TB from the time of incarceration and the time of prison release using Cox proportional hazards models. We identified 130 new TB cases diagnosed during incarceration and 170 among individuals released from prison. During imprisonment, TB rates increased from 111 cases per 100,000 person-years at entry to a maximum of 1,303 per 100,000 person-years at 5.2 years. At release, TB incidence was 229 per 100,000 person-years, which declined to 42 per 100,000 person-years (the average TB incidence in Brazil) after 7 years. We used these data to populate a compartmental model of TB transmission and incarceration to evaluate the effects of various prison-based interventions on the incidence of TB among prisoners and the general population. Annual mass TB screening within Brazilian prisons would reduce TB incidence in prisons by 47.4% (95% Bayesian credible interval [BCI], 44.4%–52.5%) and in the general population by 19.4% (95% BCI 17.9%–24.2%). A generalized model demonstrates that prison-based interventions would have maximum effectiveness in reducing community incidence in populations with a high concentration of TB in prisons and greater degrees of mixing between ex-prisoners and community members. Study limitations include our focus on a single Brazilian state and our retrospective use of administrative databases.ConclusionsOur findings suggest that the prison environment, more so than the prison population itself, drives TB incidence, and targeted interventions within prisons could have a substantial effect on the broader TB epidemic.