Starting Tuberculosis Treatment Research Articles

Effectiveness of double-dose dolutegravir in people receiving rifampin-based tuberculosis treatment: an observational, cohort study of people with HIV from six countries.

Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50 mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV. Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment. We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000 copies/mL. In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

Catastrophic costs for tuberculosis patients in India: Impact of methodological choices.

As financial risk protection is one of the goals towards universal health coverage, detailed information on costs, catastrophic costs and other economic consequences related to any disease are required for designing social protection measures. End Tuberculosis (TB) Strategy set a milestone of achieving zero catastrophic cost by 2020. However, a recent literature review noted that 7%-32% TB affected households in India faced catastrophic cost. Studies included in the review were small scale cross-sectional. We followed a cohort of 1482 notified drug-susceptible TB patients from four states in India: Assam, Maharashtra, Tamil Nadu, and West Bengal to provide a comprehensive picture of economic burden associated with TB treatment. Treatment cost was calculated using World Health Organization guidelines on TB patient cost survey and both human capital and output approaches of indirect cost (time, productivity, and income loss related to an episode) calculation were used to provide the range of households currently facing catastrophic cost. Depending on choice of indirect cost calculation method, 30%-61% study participants faced catastrophic cost. For over half of them, costs became catastrophic even before starting TB treatment as there was average 7-9 weeks delay from symptom onset to treatment initiation which was double the generally accepted delay of 4 weeks. During that period, they made average 8-11 visits to different providers and spent money on consultations, drugs, tests, and travel. Following the largest cohort of drug-susceptible TB patients till date, the study concluded that a significant proportion of study participants faced catastrophic cost and the proportion was much higher when income loss was considered as indirect cost calculation method. Therefore, ensuring uninterrupted livelihood during TB treatment is an absolute necessity. Another reason of high cost was the delay in diagnosis and costs incurred during pre-diagnosis period. This delay and consequently, economic burden, can be reduced by both supply side (intense private sector engagement, rapid diagnosis) and demand side (community engagement) initiatives. Reimbursement of expenses incurred before treatment initiation could be used as short-term measure for mitigating financial hardship.

Smoking cessation among tuberculosis patients during the coronavirus disease-2019 pandemic.

Smoking has been recognized as a significant risk factor for COVID-19 and mortality. The World Health Organization (WHO) has recommended smoking cessation to reduce the impact of COVID-19. This study aimed to evaluate the smoking cessation rate of patients starting tuberculosis (TB) treatment at six months using motivational interviewing based on the WHO "five steps to quit" model. In addition, we assessed the knowledge about smoking and the barriers to smoking cessation. We conducted a retrospective cohort study. Outpatients aged >18 years, smokers, and those who are starting TB treatment in two outpatient TB clinics were invited to participate. Patients received information about the importance of smoking cessation, especially in TB patients, and standardized advice based on guidelines. This information was repeated during phone calls during the second and fourth months of treatment. During the study period, 111 patients were included. The primary outcome was the smoking cessation rate at the end of the sixth month of treatment, which was 26.8% (19/71). The barriers to smoking cessation described by the patients were anxiety/depression (47.4%), seeing someone smoking (38.5%), drug use (19.2%), and alcohol abuse (2.6%). The assessment of knowledge about smoking showed that patients had some information gaps. In conclusion, TB smokers who tried to quit smoking during the COVID-19 pandemic faced many challenges. Despite this, we demonstrated a reasonable smoking cessation rate with a nurse-conducted motivational interview.

Epidemiology of childhood tuberculosis and predictors of death among children on tuberculosis treatment in central Ethiopia: an extended Cox model challenged survival analysis

BackgroundChildhood tuberculosis (TB) was poorly studied in Ethiopia. This study aimed to describe the epidemiology of childhood TB and identify predictors of death among children on TB treatment.MethodsThis is a retrospective cohort study of children aged 16 and younger who were treated for TB between 2014 and 2022. Data were extracted from TB registers of 32 healthcare facilities in central Ethiopia. Phone interview was also conducted to measure variables without a space and not recorded in the registers. Frequency tables and a graph were used to describe the epidemiology of childhood TB. To perform survival analysis, we used a Cox proportional hazards model, which was then challenged with an extended Cox model.ResultsWe enrolled 640 children with TB, 80 (12.5%) of whom were under the age of two. Five hundred and fifty-seven (87.0%) of the enrolled children had not had known household TB contact. Thirty-six (5.6%) children died while being treated for TB. Nine (25%) of those who died were under the age of two. HIV infection (aHR = 4.2; 95% CI = 1.9–9.3), under nutrition (aHR = 4.2; 95% CI = 2.2-10.48), being under 10 years old (aHR = 4.1; 95% CI = 1.7–9.7), and relapsed TB (aHR = 3.7; 95% CI = 1.1–13.1) were all independent predictors of death. Children who were found to be still undernourished two months after starting TB treatment also had a higher risk of death (aHR = 5.64, 95% CI = 2.42–13.14) than normally nourished children.ConclusionsThe majority of children had no known pulmonary TB household contact implying that they contracted TB from the community. The death rate among children on TB treatment was unacceptably high, with children under the age of two being disproportionately impacted. HIV infection, baseline as well as persistent under nutrition, age < 10 years, and relapsed TB all increased the risk of death in children undergoing TB treatment.

Managing Comorbidities, Determinants and Disability at Start and End of TB Treatment under Routine Program Conditions in China.

Many patients with tuberculosis (TB) have comorbidities, risk determinants and disability that co-exist at diagnosis, during and after TB treatment. We conducted an observational cohort study in 11 health facilities in China to assess under routine program conditions (i) the burden of these problems at the start and end of TB treatment and (ii) whether referral mechanisms for further care were functional. There were 603 patients registered with drug-susceptible TB who started TB treatment: 84% were symptomatic, 14% had diabetes, 14% had high blood pressure, 19% smoked cigarettes, 10% drank excess alcohol and in 45% the 6 min walking test (6MWT) was abnormal. Five patients were identified with mental health disorders. There were 586 (97%) patients who successfully completed TB treatment six months later. Of these, 18% were still symptomatic, 12% had diabetes (the remainder with diabetes failed to complete treatment), 5% had high blood pressure, 5% smoked cigarettes, 1% drank excess alcohol and 25% had an abnormal 6MWT. Referral mechanisms for the care of comorbidities and determinants worked well except for mental health and pulmonary rehabilitation for disability. There is need for more programmatic-related studies in other countries to build the evidence base for care of TB-related conditions and disability.

Burden of HIV and treatment outcomes among TB patients in rural Kenya: a 9-year longitudinal study

BackgroundAlthough tuberculosis (TB) patients coinfected with HIV are at risk of poor treatment outcomes, there is paucity of data on changing trends of TB/HIV co-infection and their treatment outcomes. This study aims to estimate the burden of TB/HIV co-infection over time, describe the treatment available to TB/HIV patients and estimate the effect of TB/HIV co-infection on TB treatment outcomes.MethodsThis was a retrospective data analyses from TB surveillance in two counties in Kenya (Nyeri and Kilifi): 2012‒2020. All TB patients aged ≥ 18 years were included. The main exposure was HIV status categorised as infected, negative or unknown status. World Health Organization TB treatment outcomes were explored; cured, treatment complete, failed treatment, defaulted/lost-to-follow-up, died and transferred out. Time at risk was from date of starting TB treatment to six months later/date of the event and Cox proportion with shared frailties models were used to estimate effects of TB/HIV co-infection on TB treatment outcomes.ResultsThe study includes 27,285 patients, median (IQR) 37 (29‒49) years old and 64% male. 23,986 (88%) were new TB cases and 91% were started on 2RHZE/4RH anti-TB regimen. Overall, 7879 (29%, 95% 28‒30%) were HIV infected. The proportion of HIV infected patient was 32% in 2012 and declined to 24% in 2020 (trend P-value = 0.01). Uptake of ARTs (95%) and cotrimoxazole prophylaxis (99%) was high. Overall, 84% patients completed six months TB treatment, 2084 (7.6%) died, 4.3% LTFU, 0.9% treatment failure and 2.8% transferred out. HIV status was associated with lower odds of completing TB treatment: infected Vs negative (aOR 0.56 (95%CI 0.52‒0.61) and unknown vs negative (aOR 0.57 (95%CI 0.44‒0.73). Both HIV infected and unknown status were associated with higher hazard of death: (aHR 2.40 (95%CI 2.18‒2.63) and 1.93 (95%CI 1.44‒2.56)) respectively and defaulting treatment/LTFU: aHR 1.16 (95%CI 1.01‒1.32) and 1.55 (95%CI 1.02‒2.35)) respectively. HIV status had no effect on hazard of transferring out and treatment failure.ConclusionThe overall burden of TB/HIV coinfection was within previous pooled estimate. Our findings support the need for systematic HIV testing as those with unknown status had similar TB treatment outcomes as the HIV infected.

Factors Associated with the Effectiveness of Regimens for the Treatment of Tuberculosis in Patients Coinfected with HIV/AIDS: Cohort 2015 to 2019.

(1) Background: Infection with the Human Immunodeficiency Virus (HIV) is a significant challenge for tuberculosis (TB) control, with increasing mortality rates worldwide. Moreover, the loss to follow-up is very high, with low adherence to treatment, resulting in unfavorable endpoints. This study aimed to analyze the effectiveness of TB treatment in patients coinfected with HIV/AIDS and its associated factors. (2) Methods: Patients coinfected with TB and HIV/AIDS at a Reference Hospital for infectious diseases were followed up for a maximum of one year from the start of TB treatment until cure or censorship (death, abandonment, and transfer) from 2015 to 2019. The Cox proportional model was used to identify risk factors for effectiveness. (3) Results: Of the 244 patients included in the cohort, 58.2% (142/244) had no treatment effectiveness, 12.3% (30/244) died, and 11.1% (27/244) abandoned treatment. Viral suppression at the onset of TB treatment (HR = 1.961, CI = 1.123-3.422), previous use of Antiretroviral Therapy (HR = 1.676, CI = 1.060-2.651), new cases (HR = 2.407, CI = 1.197-3.501), not using illicit drugs (HR = 1.763, CI = 1.141-2.723), and using the basic TB regimen (HR = 1.864, CI = 1.084-3.205) were significant variables per the multivariate Cox regression analysis. (4) Conclusion: TB treatment for most TB patients coinfected with HIV/AIDS was not effective. This study identified that an undetectable viral load at the beginning of the disease, previous use of ART, not using illicit drugs and not having previously taken anti-TB treatment are factors associated with successful TB treatment.

Characteristics of Previous Tuberculosis Treatment History in Patients with Treatment Failure and the Impact on Acquired Drug-Resistant Tuberculosis.

Tuberculosis (TB) treatment failure is a health burden, as the patient remains a source of infection and may lead to the development of multi-drug resistance (MDR). Information from cases of treatment failure that develop into MDR, which is related to a history of previous TB treatment, in accordance with the pharmacokinetic aspect, is one important thing to prevent TB treatment failure and to prevent drug resistance. This was an observational descriptive study in an acquired MDR-TB patient who had a prior history of treatment failure. A structured questionnaire was used to collect information. The questionnaire consisted of a focus on the use of TB drug formulas during the treatment period, as well as when and how to take them. This study included 171 acquired MDR-TB patients from treatment failure cases. An amount of 64 patients received the separated TB drug, and 107 patients received the fixed dose combination (FDC) TB drug. An amount of 21 (32.8%) patients receiving separated TB drug and six (5.6%) patients receiving FDC TB drug took their drug in divided doses. In addition, three (4.7%) patients receiving separated TB drug and eight (7.5%) patients receiving FDC TB drug took their drug with food. An amount of 132 out of 171 (77.2%) patients had a history of incorrect treatment that developed into MDR-TB. Education on how to take the correct medication, both the separate version and the FDC TB drug, according to the pharmacokinetic aspect, is important before starting TB treatment.

Exploring the tuberculosis medication program in Indonesia as perceived by patients and their families: A qualitative study.

Tuberculosis (TB) remains a significant public health challenge in Indonesia, with the country experiencing one of the highest numbers of lost cases in TB management. Therefore, there is a need to identify the underlying reasons for this problem. This study aimed to explore the experiences of TB-diagnosed patients and their families during the time of diagnosis and while undergoing the TB medication program. This study employed a qualitative descriptive-interpretive approach. The study was conducted in government community health centers (CHC) from May 2022 to July 2022. A total of 22 participants, consisting of 12 TB-diagnosed patients and ten family members, were included in the study. Data were collected through focus group discussions and analyzed thematically. Five themes were developed: (1) Delay in tuberculosis diagnosis, (2) Delay in starting TB treatment, (3) High willingness of patients and their families to recover, (4) Understanding that TB is an infectious disease, and (5) Factors affecting patient recovery. The study findings might contribute to the National TB elimination program. It is recommended that all health workers practicing in the community should be involved in the TB program to improve its management. Collaboration between multiple sectors in the community can also provide an advantage in solving TB problems by increasing new case detection. Additionally, it is suggested that all nurses working with TB patients establish rapport with health cadres and patients' families to enhance medication adherence in patients.

Assessment of facility-based tuberculosis data quality in an integrated HIV/TB database in three South African districts.

Assessment of data quality is essential to successful monitoring & evaluation of tuberculosis (TB) services. South Africa uses the Three Interlinked Electronic Register (TIER.Net) to monitor TB diagnoses and treatment outcomes. We assessed the quality of routine programmatic data as captured in TIER.Net. We reviewed 277 records from routine data collected for adults who had started TB treatment for drug-sensitive (DS-) TB between 10/2018-12/2019 from 15 facilities across three South African districts using three sources and three approaches to link these (i.e., two approaches compared TIER.NET with the TB Treatment Record while the third approach compared all three sources of TB data: the TB treatment record or patient medical file; the TB Identification Register; and the TB module in TIER.Net). We report agreement and completeness of demographic information and key TB-related variables across all three data sources. In our first approach we selected 150 patient records from TIER.Net and found all but one corresponding TB Treatment Record (99%). In our second approach we were also able to find a corresponding TIER.Net record from a starting point of the paper-based, TB Treatment Record for 73/75 (97%) records. We found fewer records 55/75 (73%) in TIER.Net when we used as a starting point records from the TB Identification Register. Demographic information (name, surname, date of birth, and gender) was accurately reported across all three data sources (matching 90% or more). The reporting of key TB-related variables was similar across both the TB Treatment Record and the TB module in TIER.Net (p>0.05). We observed differences in completeness and moderate agreement (Kappa 0.41-0.60) for site of disease, TB treatment outcome and smear microscopy or X-ray as a diagnostic test (p<0.05). We observed more missing items for the TB Treatment record compared to TIER.Net; TB treatment outcome date and site of disease specifically. In comparison, TB treatment start dates as well as HIV-status recording had higher concordance. HIV status and lab results appeared to be more complete in the TB module in TIER.Net than in the TB Treatment Records, and there was "good/substantial" agreement (Kappa 0.61-0.80) for HIV status. Our key finding was that the TB Module in TIER.Net was more complete in some key variables including TB treatment outcome. Most TB patient records we reviewed were found on TIER.Net but there was a noticeable gap of TB Identification patient records from the paper register as compared to TIER.Net, including those who tested TB-negative or HIV-negative. There is evidence of complete and "good/substantial" data quality for key TB-related variables, such as "First GeneXpert test result" and "HIV status." Improvements in data completeness of TIER.Net compared to the TB Treatment Record are the most urgent area for improvement, especially recording of TB treatment outcomes.

Implementation of tuberculosis and cryptococcal meningitis rapid diagnostic tests amongst patients with advanced HIV at Kamuzu Central Hospital, Malawi, 2016\u20132017

BackgroundCryptococcal meningitis (CM) and tuberculosis (TB) remain leading causes of hospitalization and death amongst people living with HIV, particularly those with advanced HIV disease. In hospitalized patients, prompt diagnosis of these diseases may improve patient outcomes. The advanced HIV rapid diagnostic tests such as determine TB urine lipoarabinomannan lateral flow assay (urine LAM), urine X-pert MTB/RIF assay (urine X-pert), and serum/blood cryptococcal antigen test (serum CrAg) are recommended but frequently not available in many resource-limited settings. We describe our experience providing these tests in a routine hospital setting.MethodFrom 1 August 2016 to 31 January 2017, a prospective cohort study to diagnose TB and Cryptococcal meningitis using point of care tests was conducted in the medical wards at Kamuzu Central Hospital, in Lilongwe, Malawi. The tests offered were PIMA CD4 cell count, serum CrAg, urine LAM, and urine X-pert. The testing was integrated into an existing HIV/TB treatment room on the wards and performed close to admission time. Patients were followed until discharge or death in the ward.ResultsWe included 438 HIV-positive patients; 76% had a previously known HIV diagnosis (87% already on ART). We measured CD4 count in 365/438 (83%), serum CrAg in 301/438 (69%), urine LAM in 363/438 (83%), and urine X-pert in 292/438 (67%). The median CD4 count was 144 cells/ml (IQR 46–307). Serum CrAg positivity rate was 23 /301 (8%) and CM was confirmed by CSF Crag in 13/23 (56%). The majority of CM patients 9/13 (69%) started antifungal therapy within two days of diagnosis. Urine LAM and urine X-pert positivity rates were 81/363(22%) and (14/292 (5%) respectively. The positivity rate of urine LAM was higher in patients with low CD4 cell counts (< 100 cells/ml) and low BMI (< 18.5). Most patients with positive urine LAM started TB treatment on the same day. Despite the early diagnosis and treatment of TB and CM, the inpatient mortality was high; 30% and 25% respectively.ConclusionAlthough advanced HIV rapid diagnostic tests are recommended, one key challenge in implementation is the limited trained personnel administering the tests. Despite the effective use of the point of care tests in the clinical care of hospitalized TB and CM patients, mortality among these patients remained unacceptably high. Henceforth we need to train other cadres apart from nurses, clinicians, and laboratory technicians to conduct the tests. There is an urgent need to identify and modify other risks of death from TB and CM.Trial registration: Malawi National Health Science Research committee: Protocol # 1144. Registered 2 July 2014 and University Of North Carolina IRB #: UNCPM 21412, approved 13th October 2014.

The utility of repeat Xpert MTB/RIF testing to diagnose tuberculosis in HIV-positive adults with initial negative result

Background: Amongst HIV-positive adults in South Africa with initial negative Xpert results, we compared the yield from repeating Xpert MTB/RIF (“Xpert”) on sputum to guideline-recommended investigation for tuberculosis (TB). Methods: A systematic sample of adults attending for HIV care were enrolled in a cohort exploring TB investigation pathways. This substudy was restricted to those at highest risk of TB (CD4&lt;200 cells/mm3 or unknown) who had a negative initial Xpert result. At attendance for the Xpert result, a repeat sputum sample was stored, and further investigations facilitated per national guidelines. Participants were reviewed monthly, with reinvestigation if indicated, for at least three months, when sputum and blood were cultured for mycobacteria, and the stored sputum tested using Xpert. We defined TB as “confirmed” if Xpert, line probe assay or Mycobacterium tuberculosis culture within six months of enrolment were positive, and “clinical” if TB treatment was started without microbiological confirmation. Results: Amongst 227 participants with an initial negative Xpert result (63% female, median age 37 years, median CD4 count 100 cells/mm3), 28 (12%) participants had TB diagnosed during study follow-up (16 confirmed, 12 clinical); stored sputum tested positive on Xpert in 5/227 (2%). Amongst 27 participants who started TB treatment, the basis was bacteriological confirmation 11/27 (41%); compatible imaging 11/27 (41%); compatible symptoms 2/27 (7%); and unknown 3/27 (11%). Conclusions: Amongst HIV-positive individuals at high risk of active TB with a negative Xpert result, further investigation using appropriate diagnostic modalities is more likely to lead to TB treatment than immediately repeating sputum for Xpert. TB diagnostic tests with improved sensitivity are needed.

Programme costs of longer and shorter tuberculosis drug regimens and drug import: a modelling study for Karakalpakstan, Uzbekistan

BackgroundThe introduction of new and often shorter tuberculosis (TB) drug regimens affects the cost of TB programmes.MethodsWe modelled drug purchase and import costs for 20-month, 9-month and 4- to 6-month TB drug regimens based on 2016–2020 treatment numbers from a TB programme in Karakalpakstan, Uzbekistan, and 2021 Global Drug Facility prices.ResultsOn average, 2225±374 (±sd) people per year started TB treatment, 30±2.1% of whom were diagnosed with drug-resistant forms of TB. Transitioning from a 6-month to a 4-month drug-susceptible (DS)-TB drug regimen increased the TB programme's annual DS-TB drug cost from USD 65±10 K to USD 357±56 K (p<0.001) and its drug import cost from USD 6.4±1.0 K to USD 9.3±1.4 K (p=0.008). Transitioning from a 20-month all-oral multidrug-resistant (MDR)-TB drug regimen to a 9-month MDR-TB drug regimen with an injectable antibiotic decreased the TB programme's annual MDR-TB drug cost from USD 1336±265 K to USD 266±53 K (p<0.001) and had no significant effect on the drug import cost (USD 28±5.5 K versus USD 27±5.4 K; p=0.88). Purchasing (USD 577±114 K) and importing (USD 3.0±0.59 K) the 6-month all-oral MDR-TB drug regimen cost more than procuring the 9-month MDR-TB drug regimen but less than the 20-month all-oral MDR-TB drug regimen (both p<0.01).ConclusionIntroducing new and shorter TB drug regimens could increase the cost of TB programmes with low drug resistance rates and decrease the cost of TB programmes with high drug resistance rates.

Patterns of non-communicable comorbidities at start of tuberculosis treatment in three regions of the Philippines: The St-ATT cohort.

Diabetes and undernutrition are common risk factors for tuberculosis (TB), associated with poor treatment outcomes and exacerbated by TB. Limited data exist describing patterns and risk factors of multiple comorbidities in persons with TB. Nine-hundred participants (69.6% male) were enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, including 133 (14.8%) initiating treatment for multi-drug resistant TB (MDR-TB). Comorbidities were defined as: diabetes, HbA1c ≥6.5% and/or on medication; hypertension, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg and/or on medication; anaemia (moderate/severe), haemoglobin <11g/dL; and, undernutrition (moderate/severe) body-mass-index <17 kg/m2. The most common comorbidities were undernutrition 23.4% (210/899), diabetes 22.5% (199/881), hypertension 19.0% (164/864) and anaemia 13.5% (121/899). Fifty-eight percent had ≥1 comorbid condition (496/847), with 17.1% having ≥2; most frequently diabetes and hypertension (N = 57, 6.7%). Just over half of diabetes (54.8%) and hypertension (54.9%) was previously undiagnosed. Poor glycemic control in those on medication (HbA1c≥8.0%) was common (N = 50/73, 68.5%). MDR-TB treatment was associated with increased odds of diabetes (Adjusted odds ratio (AOR) = 2.48, 95% CI: 1.55-3.95); but decreased odds of hypertension (AOR = 0.55, 95% CI: 0.39-0.78). HIV infection was only associated with anaemia (AOR = 4.51, 95% CI: 1.01-20.1). Previous TB treatment was associated with moderate/severe undernutrition (AOR = 1.98, 95% CI: 1.40-2.80), as was duration of TB-symptoms before starting treatment and household food insecurity. No associations for sex, alcohol or tobacco use were observed. MDR-TB treatment was marginally associated with having ≥2 comorbidities (OR = 1.52, 95% CI: 0.97-2.39). TB treatment programmes should plan for large proportions of persons requiring diagnosis and management of comorbidities with the potential to adversely affect TB treatment outcomes and quality of life. Dietary advice and nutritional management are components of comprehensive care for the above conditions as well as TB and should be included in planning of patient-centred services.

FAST tuberculosis transmission control strategy speeds the start of tuberculosis treatment at a general hospital in Lima, Peru.

Objective:To evaluate the effect of the FAST (Find cases Actively, Separate safely, Treat effectively) strategy on time to tuberculosis diagnosis and treatment for patients at a general hospital in a tuberculosis-endemic setting.Design:Prospective cohort study with historical controls.Participants:Patients diagnosed with pulmonary tuberculosis during hospitalization at Hospital Nacional Hipolito Unanue in Lima, Peru.Methods:The FAST strategy was implemented from July 24, 2016, to December 31, 2019. We compared the proportion of patients with drug susceptibility testing and tuberculosis treatment during FAST to the 6-month period prior to FAST. Times to diagnosis and tuberculosis treatment were also compared using Kaplan-Meier plots and Cox regressions.Results:We analyzed 75 patients diagnosed with pulmonary tuberculosis through FAST. The historical cohort comprised 76 patients. More FAST patients underwent drug susceptibility testing (98.7% vs 57.8%; OR, 53.8; P < .001), which led to the diagnosis of drug-resistant tuberculosis in 18 (24.3%) of 74 of the prospective cohort and 4 (9%) of 44 of the historical cohort (OR, 3.2; P = .03). Overall, 55 FAST patients (73.3%) started tuberculosis treatment during hospitalization compared to 39 (51.3%) controls (OR, 2.44; P = .012). FAST reduced the time from hospital admission to the start of TB treatment (HR, 2.11; 95% CI, 1.39–3.21; P < .001).Conclusions:Using the FAST strategy improved the diagnosis of drug-resistant tuberculosis and the likelihood and speed of starting treatment among patients with pulmonary tuberculosis at a general hospital in a tuberculosis-endemic setting. In these settings, the FAST strategy should be considered to reduce tuberculosis transmission while simultaneously improving the quality of care.

Use of prednisolone to prevent the development of immunity reconstitution syndrome in patients with multidrug-resistant tuberculosis

Inflammatory reconstitution of immune syndrome (IRIS) is an immunological reaction characterized by recurrent or new inflammatory signs of tuberculosis (TB) that occur shortly after antiretroviral therapy (ART) in 18 % of patients infected with human immunodeficiency virus (HIV). Features of the syndrome include recurrent symptoms: fever, lymphadenitis and the spread of pulmonary infiltrates on radiography. Low CD4 levels and a short interval between the onset of ART increase the risk of developing TB-associated immune system recovery syndrome. Clinical trials show that early onset of ART results in higher survival rates than ART initiated approximately 8 weeks after the start of TB treatment in patients with a CD4 count of 50 cells/μl. These findings are in line with the recommendations of the World Health Organization, which emphasize the acceleration of the onset of ART in patients with TB and low CD4 levels. However, despite the advantage of survival, early administration of ART more than increases the risk of developing IRIS associated with TB. There is no evidence-based strategy for the prevention of IRIS associated with TB. Studies evaluating adjuvant glucocorticoids for the treatment of various forms of TB have shown reduced mortality among TB patients and fewer complications among TB patients. The aim of the study was to evaluate the prophylactic use of prednisolone to safely reduce the incidence of TB-associated IRIS in patients with multidrug resistant TB (MDR TB) is at high risk of developing the syndrome. We observed HIV-infected patients who started ART (and had not previously received ART) and started TB treatment within 30 days before the start of ART and had a CD4 count of 50 cells/μl. Patients received either standard therapy with prednisolone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or only standard therapy without prednisolone. The main endpoint was the development of TB associated with TB within 12 weeks after the onset of ART. Among the 64 patients observed, the mean age was 36 years, 60 % were male, and 73 % had microbiologically confirmed TB; the median amount of CD4 was 49 cells/μl, and the median viral load was 5.5 log 10 copies/μl. Patients were divided into 2 groups. Each group included 32 patients with MDR TB / HIV co-infection. IRIS associated with TB was diagnosed in 10 patients (31.25 %) in the prednisolone group and in 17 (53.14 %) in the control group (p&lt;001). Thus, prednisolone treatment of co-infected patients with MDR TB for the first 4 weeks after the onset of HIV-related ART resulted in a lower incidence of TB-associated IRIS than in the control group, with no evidence of an increased risk of severe infections or cancer.

Radiological and functional evidence of the bronchial spread of tuberculosis: an observational analysis

SummaryBackgroundDirect bronchial spread of tuberculosis was extensively described in pre-antibiotic human pathology literature but this description has been overlooked in the post-antibiotic era, in which most pathology data come from animal models that emphasise the granuloma. Modern techniques, such as [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET-CT scans, might provide further insight. Our aim was to understand normal early tuberculosis resolution patterns on pulmonary PET-CT scans in treated patients with tuberculosis who were subsequently cured.MethodsIn this observational analysis, we analysed data from PredictTB, an ongoing, prospective, randomised clinical trial that examined sequential baseline and week 4 FDG-PET-CT scans from participants successfully treated (sputum culture negative 18 months after enrolment) for drug-susceptible pulmonary tuberculosis in South Africa and China. Participants who were aged 18–75 years, GeneXpert MTB/RIF positive for tuberculosis and negative for rifampicin resistance, had not yet started tuberculosis treatment, had not been treated for active tuberculosis within the previous 3 years, and met basic safety laboratory criteria were included and participants with diabetes, HIV infection, or with extrapulmonary tuberculosis including pleural tuberculosis were excluded. Scans were assessed by two readers for the location of tuberculosis lesions (eg, cavities and consolidations), bronchial thickening patterns, and changes from baseline to week 4 of treatment.FindingsAmong the first 124 participants (enrolled from June 22, 2017, to Sept 27, 2018) who were successfully treated, 161 primarily apical cavitary lesions were identified at baseline. Bronchial thickening and inflammation linking non-cavitary consolidative lesions to cavities were observed in 121 (98%) of 124 participants' baseline PET-CT scans. After 4 weeks of treatment, 21 (17%) of 124 participants had new or expanding lesions linked to cavities via bronchial inflammation that were not present at baseline, particularly participants with two or more cavities at baseline and participants from South Africa.InterpretationIn participants with pulmonary tuberculosis who were subsequently cured, the location of cavitary and non-cavitary lesions at baseline and new lesions at week 4 of treatment suggest a cavitary origin of disease and bronchial spread through the lungs. Bronchial spread from cavities might play a larger role in the spread of pulmonary tuberculosis than has been appreciated. Elucidating cavity lesion dynamics and Mycobacterium tuberculosis viability within cavities might better explain treatment outcomes and why some patients are cured and others relapse.FundingBill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership, China Ministry of Science and Technology, National Natural Science Foundation of China, and National Institutes of Health.TranslationsFor the Chinese, Afrikaans and Xhosa translations of the abstract see Supplementary Materials section.

Hypertension is associated with increased mortality in patients with tuberculosis in Guinea-Bissau

Tuberculosis (TB) is associated with a number of non-communicable co-morbidities, which can complicate treatment and impair outcome. The aim of this study was to assess the impact of hypertension on disease severity, treatment outcome and survival in a cohort of patients with TB. A retrospective cohort study was conducted in Guinea-Bissau. Patients newly diagnosed with TB between November 2003 and June 2016 were included. Hypertension was defined as blood pressure ≥140/90 mmHg. Disease severity was assessed using the Bandim TBscore. Survival was assessed at the end of treatment and 2 years after treatment initiation. In total, 1544 patients were included in this study. Hypertension was present in 12.8% of patients at inclusion. Patients with hypertension had slightly less severe TB, but were less likely to have a successful treatment outcome and had 64% higher mortality at 2-year follow-up (adjusted hazard ratio 1.64, 95% confidence interval 1.15-2.34). Mortality rates were highest in hypertensive female patients and patients aged ≥ 45 years. Patients with high blood pressure at the start of TB treatment had a higher mortality rate at 2-year follow-up. Mortality rates were highest in hypertensive females and patients aged ≥ 45 years.

Acceptability, feasibility, and impact of a pilot tuberculosis literacy and treatment counselling intervention: a mixed methods study

BackgroundThere is a need for innovative strategies to improve TB testing uptake and patient retention along the continuum of TB care early-on in treatment without burdening under-resourced health systems. We used a mixed methods approach to develop and pilot test a tuberculosis literacy and counselling intervention at an urban clinic in KwaZulu Natal, South Africa, to improve TB testing uptake and retention in tuberculosis care.MethodsWe engaged in discussions with clinic staff to plan and develop the intervention, which was delivered by senior social work students who received one-week training. The intervention included: 1) group health talks with all patients attending the primary clinic; and 2) individual counselling sessions, using motivational interviewing techniques, with newly diagnosed tuberculosis patients. We compared social work students’ tuberculosis knowledge, attitudes, and practices before and after their training. We assessed the change in number of tuberculosis diagnostic tests performed after implementation via an interrupted time series analysis with a quasi-Poisson regression model. We compared pre- and post-intervention probabilities of treatment initiation and completion using regression analyses, adjusting for potential baseline confounders. We conducted focus groups with the students, as well as brief surveys and one-on-one interviews with patients, to assess acceptability, feasibility, and implementation.ResultsDuring the study period, 1226 individuals received tuberculosis diagnostic testing and 163 patients started tuberculosis treatment, of whom 84 (51.5%) received individual counselling. The number of diagnostic tuberculosis tests performed increased by 1.36 (95%CI 1.23–1.58) times post-intervention, adjusting for background calendar trend. Probabilities of TB treatment initiation and treatment completion increased by 10.1% (95%CI 1.5–21.3%) and 4.4% (95%CI -7.3-16.0%), respectively. Patients found the counselling sessions alleviated anxiety and increased treatment self-efficacy. Social work students felt the clinic staff were collaborative and highly supportive of the intervention, and that it improved patient engagement and adherence.ConclusionsEngaging clinic staff in the development of an intervention ensures buy-in and collaboration. Education and counselling before and early-on in tuberculosis treatment can increase tuberculosis testing and treatment uptake. Training junior social workers can enable task-shifting in under-resourced settings, while addressing important service gaps in tuberculosis care.

Impact of the diagnostic test Xpert MTB/RIF on patient outcomes for tuberculosis.

BackgroundThe World Health Organization (WHO) recommends Xpert MTB/RIF in place of smear microscopy to diagnose tuberculosis (TB), and many countries have adopted it into their diagnostic algorithms. However, it is not clear whether the greater accuracy of the test translates into improved health outcomes.ObjectivesTo assess the impact of Xpert MTB/RIF on patient outcomes in people being investigated for tuberculosis.Search methodsWe searched the following databases, without language restriction, from 2007 to 24 July 2020: Cochrane Infectious Disease Group (CIDG) Specialized Register; CENTRAL; MEDLINE OVID; Embase OVID; CINAHL EBSCO; LILACS BIREME; Science Citation Index Expanded (Web of Science), Social Sciences citation index (Web of Science), and Conference Proceedings Citation Index ‐ Social Science & Humanities (Web of Science). We also searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Pan African Clinical Trials Registry for ongoing trials.Selection criteriaWe included individual‐ and cluster‐randomized trials, and before‐after studies, in participants being investigated for tuberculosis. We analysed the randomized and non‐randomized studies separately. Data collection and analysisFor each study, two review authors independently extracted data, using a piloted data extraction tool. We assessed the risk of bias using Cochrane and Effective Practice and Organisation of Care (EPOC) tools. We used random effects meta‐analysis to allow for heterogeneity between studies in setting and design. The certainty of the evidence in the randomized trials was assessed by GRADE.Main resultsWe included 12 studies: eight were randomized controlled trials (RCTs), and four were before‐and‐after studies. Most included RCTs had a low risk of bias in most domains of the Cochrane 'Risk of bias' tool.There was inconclusive evidence of an effect of Xpert MTB/RIF on all‐cause mortality, both overall (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.75 to 1.05; 5 RCTs, 9932 participants, moderate‐certainty evidence), and restricted to studies with six‐month follow‐up (RR 0.98, 95% CI 0.78 to 1.22; 3 RCTs, 8143 participants; moderate‐certainty evidence). There was probably a reduction in mortality in participants known to be infected with HIV (odds ratio (OR) 0.80, 95% CI 0.67 to 0.96; 5 RCTs, 5855 participants; moderate‐certainty evidence).It is uncertain whether Xpert MTB/RIF has no or a modest effect on the proportion of participants starting tuberculosis treatment who had a successful treatment outcome (OR) 1.10, 95% CI 0.96 to 1.26; 3RCTs, 4802 participants; moderate‐certainty evidence).There was also inconclusive evidence of an effect on the proportion of participants who were treated for tuberculosis (RR 1.10, 95% CI 0.98 to 1.23; 5 RCTs, 8793 participants; moderate‐certainty evidence).The proportion of participants treated for tuberculosis who had bacteriological confirmation was probably higher in the Xpert MTB/RIF group (RR 1.44, 95% CI 1.29 to 1.61; 6 RCTs, 2068 participants; moderate‐certainty evidence). The proportion of participants with bacteriological confirmation who were lost to follow‐up pre‐treatment was probably reduced (RR 0.59, 95% CI 0.41 to 0.85; 3 RCTs, 1217 participants; moderate‐certainty evidence).Authors' conclusionsWe were unable to confidently rule in or rule out the effect on all‐cause mortality of using Xpert MTB/RIF rather than smear microscopy. Xpert MTB/RIF probably reduces mortality among participants known to be infected with HIV. We are uncertain whether Xpert MTB/RIF has a modest effect or not on the proportion treated or, among those treated, on the proportion with a successful outcome. It probably does not have a substantial effect on these outcomes. Xpert MTB/RIF probably increases both the proportion of treated participants who had bacteriological confirmation, and the proportion with a laboratory‐confirmed diagnosis who were treated. These findings may inform decisions about uptake alongside evidence on cost‐effectiveness and implementation.