Starting Tuberculosis Treatment Research Articles

Efficiency of Artificial Intelligence for Interpretation of Chest Radiograms in the Republic of Tajikistan

The article presents data from recent publications and own data on screening studies with interpretation of chest radiographs using artificial intelligence CAD (Computer-Assisted Diagnosis), which, according to WHO recommendations, provides more accurate clinical thresholds for deciding who needs to take a sputum test. Another aspect of the WHO recommendations is the cost-effectiveness of CAD as a tool for triaging patients with tuberculosis symptoms in low-income countries with a high incidence of tuberculosis. Compared with smear microscopy and GeneXpert, without preliminary sorting, the use of mobile digital X-ray machines equipped with a CAD tool reduces costs, allowing sorting of individuals suspected of having tuberculosis for testing on GeneXpert, while reducing the time to start tuberculosis treatment. Thus, conducting a study using portable X-ray machines using a CAD program is a low-cost and easy-to-implement method, does not require large funds, does not require separate rooms, is highly effective, has good image quality, allows you to quickly clarify individuals suspected of having tuberculosis, differentiating it from other pathological changes in the lungs. Our experience shows that machine analysis of chest computed tomography data, due to the higher resolution capabilities of the method and the absence of fundamental disadvantages of radiography, including the effect of shadow summation, the presence of “blind” zones, etc., is finding increasing application in both diagnostics and screening of respiratory diseases. Our use of this tool allowed us to identify additional new cases of phthisio-onco-pulmonary diseases in field conditions.

Africa Health Research Institute (AHRI) Household Contact study: a study protocol, statistical analysis and modelling plan

Household case-contact studies are an established method to estimate the relative infectiousness of people with pulmonary tuberculosis. Testing of child household contacts with a QuantiFERON TB Gold plus (QFT) assay provides a proxy measure of M. tuberculosis infection in exposed household members. This study aims to generate data about the effect of antiretroviral treatment (ART) and of tuberculosis symptoms on risk of intra-household M. tuberculosis transmission to children and investigate the conditions under which symptom-agnostic screening should be considered, which could provide evidence to support a paradigm shift in tuberculosis screening strategy. Index people diagnosed with bacteriologically-confirmed pulmonary tuberculosis who have been identified by routine health services and starting tuberculosis treatment at one of the 12 health facilities serving the population of the Africa Health Research Institute health and demographic surveillance area will be eligible for recruitment. For each consenting index participant, we will enroll all household members aged 2-14 years who will undergo a symptom screen and provide a blood sample for a QFT and HIV test. We will compare the proportion of child contacts who are QFT-positive in households of (i) index adults who are living with HIV and taking ART vs not taking ART and (ii) index adults engaged in ART care who report no symptoms vs those who report symptoms. We will use a novel mathematical model, incorporating new insights into TB natural history and transmission, to determine the circumstances under which screening for TB, regardless of reported symptoms, would have most impact on tuberculosis incidence and mortality, and explore comparative cost-effectiveness of interventions along the diagnostic pathway at different levels of the health system. Estimates of relative risk of intra-household M. tuberculosis transmission, combined with healthcare utilisation and cost data, will allow us to generate mathematical model estimates of the potential epidemiological impact and relative cost-effectiveness of different approaches to tuberculosis case-finding including symptom-agnostic tuberculosis screening at different levels of the health system.

Knowledge, attitudes and practices towards tuberculosis: results of a community-based survey in the Karamoja subregion, North Eastern Uganda

BackgroundThe Karamoja subregion in north-eastern Uganda has very high Tuberculosis (TB)case notification rates and, until recently, had suboptimal treatment completion rates among patients diagnosed with TB. We evaluated community knowledge, attitudes and practices towards Tuberculosis in order to identify barriers to TB control in this region.MethodsFrom September to October 2022, we conducted a community-based survey in four districts in the Karamoja subregion. We collected data on TB knowledge, attitudes, and practices using a structured electronic questionnaire. We generated knowledge, attitude and practice scores. We used a survey-weighted zero-truncated modified Poisson model to assess the association between knowledge/attitude scores and respondents’ characteristics and a complementary log-log model to assess the association between practice scores and respondents’ characteristics. Data analysis was carried out using STATA version 14.ResultsA total of 1927 respondents were interviewed. Of these, 55.5% were female, and 1320 (68.6%) had no formal education. Overall, 68.5% 95% CI (59.6–76.7%) had knowledge scores of ≥ 60%. Higher TB knowledge scores were associated with being employed (adjusted prevalence ratio, aPR = 1.22, 95% CI 1.04–1.42, p = 0.01) while being a wife in a household was associated with lower TB knowledge (aPR = 0.90, 95% CI 0.82–0.99, p = 0.03). Being 25–34 years old was associated with a positive attitude towards TB (PR = 1.06, 1.01–1.11, p = 0.01). Over 85% of respondents would go to the health facility immediately if they had TB signs and symptoms. Almost all respondents (98.6%) would start TB treatment immediately if diagnosed with the disease.ConclusionMore than two thirds of patients had good knowledge and practices towards TB which can be leveraged to improve uptake of TB control interventions in the region. Additional interventions to improve TB knowledge and practice should focus on specific segments within the communities e.g., older women in the households.

Tuberculosis-Associated Respiratory Disability in Children, Adolescents, and Adults: Protocol for a Systematic Review and Individual Participant Data Meta-Analysis.

Approximately 2% of the global population has survived tuberculosis (TB). Increasing evidence indicates that a significant proportion of pulmonary TB survivors develop TB-associated respiratory disability, commonly referred to as post-TB lung disease (PLTD) and marked by impaired respiratory function, persistent symptoms, and activity limitations. However, the prevalence, risk factors, and progression of TB-associated respiratory disability throughout the life course are not well understood. To address these gaps, we will undertake a systematic review and individual participant-level data meta-analysis (IPD-MA) focusing on TB-associated respiratory disability in children, adolescents, and adults successfully treated for pulmonary TB. We will systematically search MEDLINE, Embase, CENTRAL, Global Index Medicus, and medRxiv for original studies investigating TB-associated respiratory disability in people of all ages who have completed treatment for microbiologically confirmed or clinically diagnosed pulmonary TB. Authors of eligible studies will be invited to contribute de-identified data and form a collaborative group. Primary outcomes will be (1) abnormal lung function based on spirometry parameters and (2) chronic respiratory symptoms. We will estimate the overall and subgroup-specific prevalence of each outcome through IPD meta-analysis. Next, we will develop clinical prediction tools assessing the risk of future TB-associated respiratory disability at (i) the start of TB treatment and (ii) end of TB treatment for those without existing signs of disability. Finally, we will use stepwise hierarchical modelling to identify epidemiological determinants of respiratory disability. This study has been approved by the ethics review boards at the Rhode Island Hospital (2138217-2) and the Research Institute of the McGill University Health Centre (2024-10345). Individual study authors will be required to obtain institutional approval prior to sharing data. Results will be disseminated through open-access, peer-reviewed publications and conference presentations. CRD42024529906.

Treatment Results in Patients with Drug Resistant Tuberculosis (MDR, pre-XDR, XDR) and HIV Infection in Stavropol Region

The objective: to compare treatment effectiveness of drug resistant tuberculosis (MDR, pre-XDR, XDR) depending on the HIV status of patients in Stavropol Region from 2019 to 2022.Subjects and Methods. In a retrospective study, chemotherapy outcomes for pulmonary tuberculosis (TB) were evaluated with distribution by treatment regimens for MDR, pre-XDR, and XDR in 100 patients with drug resistant tuberculosis (MDR, pre-XDR, XDR and HIV infection (DR TB/HIV Group ) and 707 patients with drug resistant tuberculosis (MDR, pre-XDR, and XDR) (and negative HIV status (DR TB Group). The immune status of patients in DR TB/HIV Group and its impact on the effectiveness of tuberculosis treatment were analyzed.Results. Effective treatment (definitions are given according to the Guidelines) was statistically significantly more frequently registered in DR TB Group versus DR TB/HIV Group (59% and 48%, respectively, p<0.05). Treatment failure was statistically significantly more frequently registered in patients in DR TB/HIV Group versus DR TB Group (42% and 26%, respectively, p<0.05). In DR TB/HIV Group, the lowest effectiveness (33%) of tuberculosis treatment was noted in the patients with CD4 count below 200 cells/µL. Among those died, the median time to death from the start of tuberculosis treatment was 12 months in DR TB Group, 8 months in DR TB/HIV Group, and 4 months in the subgroup of patients with CD4 count below 100 cells/µL.

Digital Adherence Technologies Linked to Mobile Money Incentives for Medication Adherence Among People Living With Tuberculosis: Mixed Methods Feasibility and Acceptability Study.

Complementing digital adherence technologies (DATs) with mobile money incentives may improve their utility in supporting tuberculosis medication adherence, yet the feasibility and acceptability of this integrated approach remain unclear. This study aims to describe the feasibility and acceptability of a novel DAT intervention called My Mobile Wallet composed of real-time adherence monitoring, SMS text message reminders, and mobile money incentives for tuberculosis medication adherence in a low-income setting. We purposively recruited people living with tuberculosis from the Mbarara Regional Referral Hospital in Mbarara, Uganda, who (1) were starting tuberculosis treatment at enrollment or within the past 4 weeks, (2) owned a mobile phone, (3) were able to use SMS test messaging, (4) were aged ≥18 years, and (5) were living in Mbarara district. At study exit (month 6), we used interviews and questionnaires informed by the unified theory of acceptance and use of technology (UTAUT) to collect feasibility and acceptability data, reflecting patients' experiences of using each component of My Mobile Wallet. Feasibility also included tracking the functionality of the adherence monitor (ie, an electronic pillbox) as well as SMS text message and mobile money delivery. We used a content analytical approach to inductively analyze qualitative data and Stata (version 13; StataCorp LLC) to analyze quantitative data. All 39 participants reported that the intervention was feasible because it was easy for them to use (eg, access and read SMS text messages) and worked as expected. Almost all SMS text messages (6880/7064, 97.4%) were sent as planned. The transmission of adherence data from the monitor worked well, with 98.37% (5682/5776) of the data transmitted as planned. All participants additionally reported that the intervention was acceptable because it helped them take their tuberculosis medication as prescribed; the mobile money incentives relieved them of tuberculosis-related financial burdens; SMS text message reminders and electronic pillbox-based alarms reminded them to take their medication on time; and participants perceived real-time adherence monitoring as "being watched" while taking their medication, which encouraged them to take their medication on time to demonstrate their commitment. The intervention was perceived as a sign of care, which eventually created emotional support and a sense of connectedness to health care. Participants preferred daily SMS text message reminders (32/39, 82%) to reminders linked to missed doses (7/39, 18%), citing the fact that tuberculosis medication is taken daily. The use of real-time adherence monitoring linked to SMS text message reminders and mobile money incentives for tuberculosis medication adherence was feasible and acceptable in a low-resource setting where poverty-based structural barriers heavily constrain tuberculosis treatment and care.

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.

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.

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.

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.