How can tuberculosis services better support patients with a diabetes co-morbidity? A mixed methods study in the Philippines.

BACKGROUND: People with diabetes mellitus (DM) have an estimated two- to three-times greater risk of adverse tuberculosis (TB) treatment outcomes compared to those without DM. Blood glucose control is a primary aim of managing DM during TB treatment, yet TB programmes are not generally adapted to provide DM services. The purpose of this study was to understand perceptions and the lived experiences of diabetic patients in TB treatment in the Philippines, with a view to informing the development of disease co-management strategies. METHODS: This mixed methods study was conducted within a prospective cohort of adults newly-starting treatment for drug-sensitive and drug-resistant TB at 13 public TB clinics in three regions of the Philippines. Within the subset of 189 diabetic persons who self-reported a prior DM diagnosis, or were diagnosed by screenings conducted through the TB clinic, longitudinal blood glucose data were used to ascertain individuals' glycaemic control (controlled or uncontrolled). Univariable logistic regression analyses exploring associations between uncontrolled glycaemia and demographic and clinical factors informed purposive sampling of 31 people to participate in semi-structured interviews. All audio-recorded data were transcribed and thematic analysis performed. RESULTS: Participants - both with controlled and uncontrolled blood glucose - were knowledgeable about diabetes and its management. However, a minority of participants were aware of the impact of DM on TB treatment and outcomes. Many participants newly-diagnosed with DM at enrolment in TB treatment had not perceived any diabetic symptoms prior and would have likely not sought clinical consult otherwise. Access to free glucose-lowering medications through TB clinics was a key enabling resource. However, participants expressed fear of side effects and interrupted access to glucose-lowering medications, and a preference for phytotherapy. Many participants felt that physical and financial impacts of TB and its treatment were challenges to DM management. CONCLUSIONS AND RECOMMENDATIONS: Results of this study indicate that public TB clinics can provide diabetic patients with additional health care resources and education to address co-morbidity. TB programmes might consider identifying patients with complicated DM, and offering diabetic monitoring and management, as DM and diabetic complications may compound the burden of TB and its treatment.

Gender differences in tuberculosis patients with comorbidity: A cross-sectional study using national surveillance data and national health insurance claims data in South Korea.

The coexistence of tuberculosis and other chronic diseases complicates disease management. Particularly, the lack of information on the difference in the prevalence of chronic diseases in tuberculosis based on age and gender can hinder the establishment of appropriate public health strategies. This study aimed to identify age- and gender-based differences in the prevalence of chronic diseases as comorbidities in patients with tuberculosis. An anonymized data source was established by linking the national health insurance claims data to the Korean national tuberculosis surveillance data from 2014 to 2018. The prevalence of chronic diseases was stratified by gender and age (age groups: ≤64, 65-74, and ≥75 years), and the differences in the prevalence of chronic diseases were analyzed by multinomial logistic regression and classified using the Charlson Comorbidity Index. A total of 148,055 patients with tuberculosis (61,199 women and 86,856 men) were included in this study. Among the patients aged ≥65 years, 48.2% were female and 38.1% were male. In this age group, the probability of chronic disease comorbidity was higher in female patients than in male patients. The prevalence of congestive heart failure and dementia as comorbidities in patients with tuberculosis increased more drastically with age in women than in men. Thus, the present study confirmed gender and age differences in the distribution of comorbidities among patients with tuberculosis. A more comprehensive gender-responsive approach for patients with tuberculosis and chronic diseases is required to alleviate the double burden of infectious diseases and non-communicable diseases in an aging society.

Cross-sectional study of nutritional intake among patients undergoing tuberculosis treatment along the Myanmar-Thailand border.

OBJECTIVE: This study summarises nutritional intake among patients with tuberculosis (TB) along the Myanmar-Thailand border according to the local diet. SETTING: TB clinic along the Myanmar-Thailand border. PARTICIPANTS: Cross-sectional surveys of 24-hour food recall were conducted with participants receiving anti-TB treatment. Participants were purposively selected to reflect proportion of age, sex and HIV co-infection based on historical patient records. Out of a total of 28 participants, 20 (71.4%) were men and 5 (17.9%) were co-infected with HIV. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome compared actual recorded intake to recommended intake. Secondary outcomes compared weight gain and body mass index (BMI) from diagnosis to time of survey. RESULTS: There were no significant differences in macronutrient or micronutrient intake by sex or for patients supplementing their rations. Mean treatment length at time of survey was 20.7 weeks (95% CI: 16.5 to 24.8). A significantly higher proportion of women (8/8, 100%) met caloric requirements compared with men (9/20, 45.0%, p=0.010), but few participants met other macronutrient or micronutrient requirements, with no significant differences by sex or for patients supplementing their rations. From diagnosis to the time of the survey, participants averaged significant weight gain of 6.48 kg (95% CI: 3.87 to 9.10) and increased BMI of 2.47 kg/m2 (95% CI: 1.45 to 3.49; p=0.0001 for both). However, 50% (14/28) still had mild or more severe forms of malnutrition. CONCLUSIONS: This cross-sectional survey of nutritional intake in patients undergoing TB treatment in a sanatorium setting demonstrates the difficulty in sufficiently meeting nutritional demands, even when providing nutritional support.

Bidirectional screening and treatment outcomes of diabetes mellitus (DM) and Tuberculosis (TB) patients in hospitals with measures to integrate care of DM and TB and those without integration measures in Malawi.

INTRODUCTION: There are efforts in low and middle-income countries (LMICs) to integrate Tuberculosis (TB) and Diabetes mellitus (DM) healthcare services, as encouraged by WHO and other international health organizations. However, evidence on actual effect of different integration measures on bidirectional screening coverages and or treatment outcomes for both diseases in LMICs is scarce. OBJECTIVES AND METHODS: Retrospective chart review analysis was conducted to determine effects of integrated care on bidirectional screening and treatment outcomes for both TB patients and people with DM (PWD) recruited in eight Malawian hospitals. Data of ≥ 15 years old patients registered between 2016 to August 2019 were collected and analysed. RESULTS: 557 PWDs (mean age 54) and 987 TB patients (mean age 41) were recruited. 64/557 (11.5%) PWDs and 105/987 (10.6%) of TB patients were from an integrating hospital. 36/64 (56.3%) PWDs were screened for TB in integrated healthcare as compared to 5/493 (1.0%) in non-integrated care; Risk Difference (RD) 55.2%, (95%CI 43.0, 67.4), P < 0.001, while 10/105 (9.5%) TB patients were screened for DM in integrated healthcare as compared to 43/882 (4.9%) in non-integrated care; RD 4.6%, (95%CI - 1.1, 10.4), P = 0.065. Of the PWDs screened, 5/41 (12.2%) were diagnosed with TB, while 5/53 (9.4%) TB patients were diagnosed with DM. On TB treatment outcomes, 71/508 (14.8%) were lost to follow up in non-integrated care and none in integrated care were lost to follow-up; RD - 14.0%, (95%CI: - 17.0,-11.0), p < 0.001. Among PWDs, 40/493 (8.1%) in non-integrated care and 2/64 (3.1%) were lost to follow up in integrated care; RD - 5.0%, (95%CI:-10.0, - 0.0); P = 0.046. After ≥ 2 years of follow up, 62.5% PWDs in integrated and 41.8% PWDs in non-integrated care were retained in care, RD 20.7, (95%CI: 8.1, 33.4), P = 0.001. CONCLUSION: We found higher bidirectional screening coverage and less loss to follow-up in one centre that made more efforts to implement integrated measures for TB and DM care than in 7 others that did not make these efforts. Decisions on local programs to integrate TB/DM care should be taken considering currently rather weak evidence and barriers faced in the local context as well as existing guidelines.

Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine.

BACKGROUND: A 4-month regimen containing rifapentine and moxifloxacin has noninferior efficacy compared to the standard 6-month regimen for drug-sensitive tuberculosis. We evaluated the effect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral suppression in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB). METHODS: In the context of a Phase 3 randomized controlled trial, HIV-positive individuals already virally suppressed on efavirenz--containing antiretroviral therapy (ART) (EFV1), or newly initiating efavirenz (EFV2) received TB treatment containing rifapentine (1200 mg), isoniazid, pyrazinamide, and either ethambutol or moxifloxacin. Mid-interval efavirenz concentrations were measured (a) during ART and TB cotreatment (Weeks 4, 8, 12, and 17, different by EFV group) and (b) when ART was taken alone (pre- or post-TB treatment, Weeks 0 and 22). Apparent oral clearance (CL/F) was estimated and compared. Target mid-interval efavirenz concentrations were > 1 mg/L. Co-treatment was considered acceptable if > 80% of participants had mid-interval efavirenz concentrations meeting this target. RESULTS: EFV1 and EFV2 included 70 and 41 evaluable participants, respectively. The geometric mean ratio comparing efavirenz CL/F with vs without TB drugs was 0.79 (90% confidence interval [CI] .72-.85) in EFV1 and 0.84 [90% CI .69-.97] in EFV2. The percent of participants with mid-interval efavirenz concentrations > 1mg/L in EFV1 at Weeks 0, 4, 8, and 17 was 96%, 96%, 88%, and 89%, respectively. In EFV2, at approximately 4 and 8 weeks post efavirenz initiation, the value was 98%. CONCLUSIONS: TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) efavirenz clearance and therapeutic targets were met supporting the use of efavirenz with these regimens, without dose adjustment. CLINICAL TRIALS REGISTRATION: NCT02410772.

Adjunctive vitamin A and D for the glycaemic control in patients with concurrent type 2 diabetes and tuberculosis: a randomised controlled trial.

The objective of this study is to investigate the effects of vitamin A, D and their interaction on the glycaemic control in patients with both diabetes and tuberculosis. Tuberculosis infection and its treatment induce hyperglycaemia and complicate the glycaemic control in patients with diabetes. A randomised controlled trial with a 2 × 2 factorial design was conducted in a tuberculosis-specialised hospital in Qingdao, China. A total of 279 patients who have both diabetes and tuberculosis were included in this analysis. The patients received standard anti-tuberculosis treatment alone (control group), or together with a dose of vitamin A (600 µg RAE/d) or vitamin D (10 µg/d) or a combination of vitamin A (600 µg RAE/d) and vitamin D (10 µg/d) for 2 months. The effects of the intervention on fasting plasma glucose and 2-h postprandial blood glucose were investigated by ANCOVA. The analysis was adjusted for baseline values, age, sex, smoking, drinking and antidiabetic treatment as covariates. No significant effect was observed for vitamin A and D supplementation on fasting plasma glucose, 2-h postprandial blood glucose, BMI and related blood parameters. No interaction was observed between vitamin A and D supplementation for these endpoints. Vitamin A and D supplementation showed a null effect on the glycaemic control for patients with concurrent diabetes and tuberculosis. Future work should evaluate the effect of vitamin A and D supplementation on insulin-related indices for these patients and investigate the effect of vitamin D receptor genotypes.

Effect of Vitamin D Supplementation in Type 2 Diabetes Patients with Tuberculosis: A Systematic Review.

BACKGROUND: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity. OBJECTIVE: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients. METHOD: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review. RESULT: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant. CONCLUSION: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population.

Terapias biológicas y tuberculosis en pediatría / Biological therapies and tuberculosis in pediatrics

En los últimos años, ha habido un aumento sostenido del uso de terapias inmunomoduladoras como las terapias biológicas y en un período más reciente, de las terapias con moléculas pequeñas. Estos tratamientos constituyen un factor de riesgo más para enfermar de tuberculosis en adultos y aunque en menor grado, también en niños, especialmente con el uso de anti TNF-α, por lo que antes de iniciar una terapia biológica, hay que descartar la tuberculosis activa y la latente. En el tratamiento de una tuberculosis activa producida por un biológico se debe prolongar la etapa de continuación a 9 meses. Es importante el seguimiento clínico prolongado en años de quienes usan o han completado el uso de estas terapias. Hay que posponer la vacunación BCG en los hijos de madres que usaron terapias biológicas durante la gestación hasta la edad 6 a 12 meses de los niños. El foco de esta revisión está centrado en la tuberculosis por progresión de una forma latente a una activa o por un contacto estrecho con una persona con tuberculosis pulmonar en pacientes que reciben terapias biológicas anti TNF alfa de uso inmunoreumatológico.

In recent years, there has been a sustained increase in the use of immunomodulatory therapies such as biologic therapies and, more recently, small molecule therapies. Those therapies have become another risk factor for tuberculosis in adults and, although to lesser degree, also in children, especially some of them, such as anti-TNF α. Before starting biological therapy, active tuberculosis and latent tuberculosis must be ruled out. In the treatment of active tuberculosis caused by a biologic, the continuation stage should be extended to 9 months. Long-term clinical follow-up in years of those who use them or have completed their use, is important. BCG vaccine should be postponed in children of mother who used biologic therapies during pregnancy until the children ́s age 6 to 12 months. The focus of this review is centered on tuberculosis due to progression from a latent to an active form or due to close contact with a person with pulmonary tuberculosis in patients receiving anti-TNF alpha biological therapies for immunorheumatology use.

Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis.

BACKGROUND AND AIMS: Post-tuberculosis bronchial stenosis (PTBS) is one of the most common complications of tracheobronchial tuberculosis. Silicone stent serves as a major treatment for maintaining airway patency. However, silicone stent placement remains a large challenge in patients with severe cicatricial PTBS. Our objective was to evaluate the efficacy and safety of covered, self-expanding, metallic stents (SEMSs) as a transition to silicone stent implantation for treating severe PTBS. METHODS: We retrospectively reviewed the data of patients with severe PTBS who received airway stenting in the First Affiliated Hospital of Guangdong Medical University between September 2015 and May 2019. The types of the stent, intervention procedures, bronchoscopic findings, clinical outcomes and related complications were collected and analyzed. RESULTS: Fifty-eight cases with severe PTBS were included in this study. Thirteen (22.4%) of the patients received bronchial silicone stent implantation immediately after dilations. For the remaining 45 (77.6%) patients, silicone stents could not be deployed after dilations and SEMSs implantation was implemented as a bridge to silicone stenting. The SEMSs were placed for an interval of 28.4 ± 11.1 days. All of the silicone stents were inserted successfully following the removal of SEMSs. No SEMS-related complication occurred. The subgroup analysis showed that patients who received transitional SEMSs had less luminal caliber but fewer transbronchial dilations before silicone stent implantation (p < 0.05). CONCLUSION: Covered SEMS placement as a transition to silicone stenting could serve as a feasible procedure to reduce complications and improve the success rate of silicone stent implantation in patients with severe PTBS.The reviews of this paper are available via the supplemental material section.

Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis.

Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during antituberculosis treatment to support hemoglobin (Hb) recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, as well as changes in inflammation and iron metabolism indices. In a 26-week prospective study, Tanzanian adults with tuberculosis (N = 18) were studied before treatment and then every 2 weeks during treatment; oral and intravenous iron tracers were administered before treatment and after intensive phase (8/12 weeks) and complete treatment (24 weeks). No iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (∼80%), and iron absorption was negligible (<1%). During treatment, hepcidin and interleukin-6 levels decreased ∼70% after only 2 weeks (P< .001); in contrast, ERFE did not significantly decrease until 8 weeks (P< .05). ERFE and interleukin-6 were the main opposing determinants of hepcidin (P< .05), and greater ERFE was associated with reticulocytosis and Hb repletion (P< .01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (P< .01), indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ∼20-fold (P< .001), and Hb increased ∼25% (P< .001). In tuberculosis-associated anemia of inflammation, our findings suggest that elevated ERFE is unable to suppress hepcidin, and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well absorbed only after tuberculosis treatment, and supplementation should be reserved for patients remaining anemic after treatment. This trial was registered at www.clinicaltrials.gov as #NCT02176772.

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1ß, and TNF-α. Fe lowered lung IL-1α, IL-1ß, plasma IL-1ß, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

Barriers to and enablers of uptake of and adherence to antiretroviral therapy in the context of integrated HIV and tuberculosis treatment among adults in sub-Saharan Africa: a protocol for a systematic literature review.

INTRODUCTION: The scale-up of integrated Human Immunodeficiency Virus (HIV) and tuberculosis (TB) treatment has been an important intervention to curb the burden of HIV and TB co-infection worldwide. Uptake of and adherence to antiretroviral therapy (ART) are key determinants of the quality and therapeutic endpoints of this intervention. This study aims to conduct an up-to-date collection and synthesis of evidence on barriers to and facilitators of uptake of and adherence to ART in HIV/TB integrated treatment programs in sub-Saharan Africa (SSA). METHOD: A systematic review of peer-reviewed literature on the uptake of and adherence to ART in the context of integrated therapy for HIV and TB in SSA will be performed. We will review qualitative and quantitative studies reporting on the uptake of and adherence to ART during integrated treatment for TB and HIV among adults. These will include studies that involve HIV-infected TB patients initiating ART and studies involving PLWHA already on ART who are newly diagnosed with TB. Qualitative studies, quantitative studies, randomised trials and observational studies will be included. Six databases including Medline and Embase will be searched for relevant studies published from March 2004 to July 2019. Two authors will independently screen the search output and retrieve full texts of eligible studies. Disagreements between the two authors will be resolved by arbitration by a third author. Data will be abstracted from the eligible studies and synthesis will be done through descriptive synthesis for qualitative data and meta-analysis for quantitative data. ETHICS AND DISSEMINATION: This study will be a review of the literature and will not involve primary collection of individuals' data. Amendments to the protocol will be documented in the final review. The final study will be published in a peer-reviewed journal and presented at conferences. The review is expected to contribute to improving strategies to enhance uptake of and adherence to ART in integrated care. PROSPERO REGISTRATION NUMBER: CRD42019131933.

Delays to anti-tuberculosis treatment intiation among cases on directly observed treatment short course in districts of southwestern Ethiopia: a cross sectional study.

BACKGROUND: Delayed tuberculosis (TB) diagnosis and treatment increase morbidity, mortality, expenditure, and transmission in the community. This study assessed patient and provider related delays to diagnosis and treatment of TB. METHODS: A cross-sectional study was conducted among 735 new adult TB cases registered between January to December 2015 in 10 woredas equivalent to districts of southwestern Ethiopia. Data were collected through face-to-face interview of patients within the first 2 months of treatment initiation. Delay in days was tracked at three intervals: between onset of symptoms and self-presentation (Patient delay), Self-presentation to treatment initiation (Provider delay) and total delay. Days elapsed beyond median were used to define the delays. Bivariate and multiple logistic regression models were fit to identify predictors of delays and statistical significance was judged at p < 0.05. RESULT: The median (inter-quartile range) of patient, provider and total delays were 25 (IQR;15-36), 22 (IQR:9-48) and 55 (IQR:32-100) days, respectively. More than half (54.6%) of the total delay was attributed to health system. Prior self-treatment [adjusted Odds Ratio (aOR)]: 1.72, 95% confidence interval [CI]:1.07-2.75), HIV co-infection (aOR:1.8, 95% CI: 1.05-3.10) and extra-pulmonary TB (aOR: 1.54,95% CI:1.03-2.29) were independently associated with increased odds of patient delay. On the other hand initial presentation to health posts or private clinics (aOR: 1.42, 95% CI: 1.01, 2.0) and patient delay (aOR: 1.81, 95% CI: 1.33-2.50) significantly predicted longer provider delay. Finally, having extra pulmonary TB (aOR: 1.6, 95% CI: 1.07-2.38), prior consultation of traditional healer (aOR: 3.72, 95% CI: 1.01-13.77) and use of holy water (aOR: 2.73, 95% CI: 1.11, 6.70) independently predicted longer total delay. CONCLUSION: Tuberculosis patients waited too long time to initiate anti-TB treatment reflecting longer periods of morbidity and disease transmission. The delays are attributed to the patient, disease and health system related factors. Hence, improving community awareness, involving informal providers, health extension workers and TB treatment supporters can reduce the patient delay. Similarly, cough screening and improving diagnostic efficiencies of healthcare facilities should be in place to reduce the provider delays.

Integrated care of severe infectious diseases to people with substance use disorders; a systematic review.

BACKGROUND: Various integrated care models have been used to improve treatment completion of medications for chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV), Mycobacterium tuberculosis (TB), and Human immunodeficiency virus (HIV) among people with substance use disorders (SUD). We have conducted a systematic review to evaluate whether integrated models have impacts of the treatment of infectious diseases among marginalized people with SUD. METHODS: We searched MEDLINE/PubMed (1946 to 2018, on July 26, 2018) and Embase (from 1974 to 2018, on July 26, 2018) for randomized controlled trials (RCTs) and cohort studies evaluating diverse integrated models' effects on sustained virological response (SVR), HIV suppression, HBV curation or suppression, completion of TB treatment regimen among people with SUD. The included studies were assessed qualitatively. RESULTS: Altogether, 1640 studies, and references to 1135 related reviews and RCTs were considered, and only seven RCTs and three cohort studies fulfilled the inclusion criteria. We identified nine integrated care models. Two studies, one RCT and one cohort study, showed a significant effect of their integrated models. The RCT evaluated psychosocial treatment, opioid agonist treatment (OAT) and directly observed TB treatment, and found a significant increase in TB treatment completions among intervention group compared to control group (60% versus 13%, p < 0.01). The cohort study including OAT and TB treatments had an effect on TB treatment completion in hospitalized patients (89% versus 73%, p = 0.03). Eight out of ten studies showed no significant effects of their integrated care models on defined outcomes. One of which having included 363 participants in a RCT showed no effect on SVR compared to the control group when the results adjusted for active substance use and alcohol dependence in a post-hoc analysis (11% versus 7%, p = 0.49). CONCLUSIONS: The findings indicate uncertainty on the effects of integrated care models' on treatment for severe infectious diseases among people with SUD. Some studies point toward that integrated models could improve care of people with SUD, yet high-quality studies and preferably, sufficiently sized clinical trials are needed to conclude on the degree of impact.

The potential of plant systems to break the HIV-TB link.

Tuberculosis (TB) and human immunodeficiency virus (HIV) can place a major burden on healthcare systems and constitute the main challenges of diagnostic and therapeutic programmes. Infection with HIV is the most common cause of Mycobacterium tuberculosis (Mtb), which can accelerate the risk of latent TB reactivation by 20-fold. Similarly, TB is considered the most relevant factor predisposing individuals to HIV infection. Thus, both pathogens can augment one another in a synergetic manner, accelerating the failure of immunological functions and resulting in subsequent death in the absence of treatment. Synergistic approaches involving the treatment of HIV as a tool to combat TB and vice versa are thus required in regions with a high burden of HIV and TB infection. In this context, plant systems are considered a promising approach for combatting HIV and TB in a resource-limited setting because plant-made drugs can be produced efficiently and inexpensively in developing countries and could be shared by the available agricultural infrastructure without the expensive requirement needed for cold chain storage and transportation. Moreover, the use of natural products from medicinal plants can eliminate the concerns associated with antiretroviral therapy (ART) and anti-TB therapy (ATT), including drug interactions, drug-related toxicity and multidrug resistance. In this review, we highlight the potential of plant system as a promising approach for the production of relevant pharmaceuticals for HIV and TB treatment. However, in the cases of HIV and TB, none of the plant-made pharmaceuticals have been approved for clinical use. Limitations in reaching these goals are discussed.

Active Tuberculosis in Patients with Psoriasis Receiving Biologic Therapy: A Systematic Review.

BACKGROUND: Biologic therapies pose a risk for opportunistic infections, especially for reactivating latent tuberculosis infection (LTBI). OBJECTIVE: The aim was to describe the clinical features and mortality rate of active Mycobacterium tuberculosis (TB) in psoriasis patients receiving biologic therapies. METHODS: A systematic review of PubMed, Google Scholar, ScienceDirect, Cochrane Library, and ClinicalTrials.gov databases was performed. Studies describing active TB in patients with psoriasis receiving biologic therapy from inception to May 31, 2018 were included. Clinical data as well as mortality rates were recorded. RESULTS: Fifty-one studies were included, evaluating 78 patients with active TB: 11 prospective studies, 13 retrospective, and 27 case reports/series. Most patients (73%) with active TB were male, the mean age was 48 ± 13 years, and 85% were of European or Asian origin. Pre-treatment LTBI screening was negative for 63% of patients. Disease presented in 33% of patients within the first 3 months of treatment, and in 51% within the first 6 months. Most patients (72%) presented with extra-pulmonary TB, and 49% had disseminated disease. The mortality rate was 7%. LIMITATIONS: Limitations of this review are its small sample size and inclusion of case reports. CONCLUSIONS: Some patients develop active TB despite LTBI screening. Clinicians initiating biologic therapy in patients with psoriasis should be aware of the clinical features of active TB in this scenario.

Ischemic stroke and disseminated tuberculosis in a child living with human immunodeficiency virus: a case report and review of the literature.

BACKGROUND: Cerebrovascular accidents are rare in children. Rates of stroke in children with human immunodeficiency virus infection are higher than in the uninfected population. CASE PRESENTATION: We report the case of a 19-month-old Ethiopian boy who presented with a left-sided body weakness of sudden onset. He was also diagnosed as having human immunodeficiency virus infection. Laboratory tests showed an iron deficiency anemia and imaging revealed tuberculosis of his lungs, spleen, and abdominal lymph nodes as well as an acute ischemic stroke of the right middle cerebral artery region. His symptoms improved after anti-tuberculosis drugs, antiretroviral treatment, and iron supplementation were initiated. CONCLUSIONS: Extrapulmonary tuberculosis should be considered a cause of sudden focal neurologic deficits in children with human immunodeficiency virus infection residing in endemic countries.