Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

BACKGROUND: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear. METHODS: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis. RESULTS: No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons). CONCLUSIONS: Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).

Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: In most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy. METHODS: In this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days. RESULTS: We enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3. CONCLUSIONS: The administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.).

Costs of Digital Adherence Technologies for Tuberculosis Treatment Support, 2018-2021.

Digital adherence technologies are increasingly used to support tuberculosis (TB) treatment adherence. Using microcosting, we estimated healthcare system costs (in 2022 US dollars) of 2 digital adherence technologies, 99DOTS medication sleeves and video-observed therapy (VOT), implemented in demonstration projects during 2018-2021. We also obtained cost estimates for standard directly observed therapy (DOT). Estimated per-person costs of 99DOTS for drug-sensitive TB were $98 in Bangladesh (n = 719), $119 in the Philippines (n = 396), and $174 in Tanzania (n = 976). Estimated per-person costs of VOT were $1,154 in Haiti (87 drug-sensitive), $304 in Moldova (173 drug-sensitive), $452 in Moldova (135 drug-resistant), and $661 in the Philippines (110 drug-resistant). 99DOTS costs may be similar to or less expensive than standard DOT. VOT is more expensive, although in some settings, labor cost offsets or economies of scale may yield savings. 99DOTS and VOT may yield savings to local programs if donors cover infrastructure costs.

Acceptability of an automated directly observed therapy (DOT) application for PrEP adherence support among young men who have sex with men: a qualitative exploration.

Pre-exposure prophylaxis (PrEP) adherence remains a challenge among young men who have sex with men (MSM). We developed and tested a smartphone application ("app"), "DOT Diary", which combines automated directly observed therapy (DOT) with information about PrEP protection levels, pill-taking reminders, a sexual behavior diary, and a PrEP dosing calendar. To contextualize trial results, we qualitatively explored participants' app experiences. The trial enrolled 100 young MSM in San Francisco and Atlanta. Participants were randomized 2:1 to DOT Diary versus standard-of-care and followed for 24 weeks. Interviews were conducted with 24 intervention participants. Data were analyzed using a memo-writing approach. Most expressed overall satisfaction with the app ("it was good for its purpose"), despite concerns about technical glitches. The most popular app features were the monthly calendar showing days PrEP was taken and information about level of protection based on pills taken. The DOT component helped participants establish PrEP routines. The reminders were "annoying but effective" at motivating dosing. Opinions about the sexual behavior diary varied. Overall, DOT Diary was acceptable; participants were willing to use it daily to record pill-taking. Critical components included the information about PrEP protection levels and calendar, while others may be modified to improve future success.Trial registration: ClinicalTrials.gov identifier: NCT03771638.

Tuberculosis treatment delay and associated factors among pulmonary tuberculosis patients at public health facilities in Dale District and Yirgalem Town administration, Sidama Region, South Ethiopia.

BACKGROUND: Tuberculosis (TB) treatment delay is one of the major challenges of TB care in many low-income countries. Such cases may contribute to an increased TB transmission and severity of illness. The aim of this study was to determine the magnitude of patient delay in TB treatment, and associated factors in Dale District and Yirgalem Town administration of Sidama Region, Southern Ethiopia. METHODS: Between January 1-Augst 30/ 2022, we studied randomly selected 393 pulmonary TB cases on Directly Observed Treatment Short course (DOTS) in Dale District and Yirgalem Town Administration. After conducting a pretest, we interviewed participants on sociodemographic, health seeking behavior and clinical factors and reviewed the TB registry. Trained enumerators interviewed to collect data. We entered data in to EPI-info 7 version 3.5.4 and then exported to the Statistical Package for Social Science (SPSS) version 23 for analysis. Multivariable logistic regression was used to identify associated factors of TB and statistical significance was defined using the 95% confidence interval. RESULT: A total of 393 (98%) participants involved in the study. The magnitude of delay in TB treatment among the study participants was 223 (56.7%) (95% CI (51.8 - 61.6%)). Distance of the health facility from home, (adjusted odds ratio (AOR) = 2.04, 95% CI (1.3, 3.2)), seeking antibiotic treatment before being diagnosed for TB (AOR = 2.1, 95% CI (1.3, 3.5)) and the knowledge of TB prevention and treatments (AOR = 5.9, 95% CI (3.6, 9.8)), were factors associated with delay in TB treatment. CONCLUSION: The prevalence of TB treatment delay among pulmonary TB patients in the study setting was high. Delay in TB treatment was associated with knowledge, behavioral and accessibility related factors. Providing health education and active case finding of TB would help in minimizing the delay.

Predictors of unsuccessful tuberculosis treatment outcomes in Brazil: an analysis of 259,484 patient records.

INTRODUCTION: Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. METHODS: We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment. RESULTS: Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT). CONCLUSION: The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil.

Understanding the role of video direct observed therapy for patients on an oral short-course regimen for multi-drug resistant tuberculosis: findings from a qualitative study in Eswatini.

BACKGROUND: Improving treatment success rates among multi drug-resistant tuberculosis (MDR-TB) patients is critical to reducing its incidence and mortality, but adherence poses an important challenge. Video-based direct observed therapy (vDOT) may provide adherence benefits, while addressing the time and cost burden associated with community treatment supporter (CTS)-DOT. This study explored experiences of patients, family members and healthcare workers with different DOT modalities for adherence support in Eswatini. METHODS: Between April 2021 and May 2022, thirteen men and five women with MDR-TB, ten healthcare workers, and nine caregivers were purposively sampled to include a range of characteristics and experiences with DOT modalities. Data were generated through individual in-depth interviews and a smartphone messaging application (WhatsApp). Data coding was undertaken iteratively, and thematic analysis undertaken, supported by Nvivo. RESULTS: Four themes emerged that reflected participants' experiences with different DOT modalities, including stigma, efficiency, perceived risks of TB acquisition, and patient autonomy. vDOT was appreciated by patients for providing them with privacy and shielding them from stigmatisation associated with being seen in TB clinics or with community treatment supporters. vDOT was also seen as more efficient than CTS-DOT. Health workers acknowledged that it saved time, allowing them to attend to more patients, while many patients found vDOT more convenient and less expensive by removing the need to travel for in-person consultations. Health workers also appreciated vDOT because it reduced risks of TB acquisition by minimising exposure through virtual patient monitoring. Although many patients appreciated greater autonomy in managing their illness through vDOT, others preferred human contact or struggled with making video recordings. Most family members appreciated vDOT, although some resented feeling removed from the process of supporting loved ones. CONCLUSIONS: vDOT was generally appreciated by MDR-TB patients, their family members and health workers as it addressed barriers to adherence which could contribute to improved treatment completion rates and reduced workplace exposure. However, patients should be offered an alternative to vDOT such as CTS-DOT if this modality does not suit their circumstances or preferences.

Understanding the impact of pandemics on long-term medication adherence: directly observed therapy in a tuberculosis treatment cohort pre- and post-COVID-19 lockdowns.

BACKGROUND: The COVID-19 pandemic negatively impacted tuberculosis (TB) treatment services, including directly observed therapy (DOT) programs used to promote medication adherence. We compared DOT adherence embedded in a research study before and after COVID-19 lockdowns in South Africa. METHODS: We analyzed data from 263 observational study participants undergoing drug susceptible (DS)-TB DOT between May 2017 to March 2022. Participants enrolled before October 2019 were considered 'pre-COVID-19' and those enrolled after September 2020 were considered 'post-COVID-19 lockdown groups. Negative binomial regression models were used to compare DOT non-adherence rates between the two lockdown groups. We then conducted a sensitivity analysis which only included participants enrolled in the immediate period following the first COVID-19 lockdown. RESULTS: DOT non-adherence rate was higher in the post-COVID-19 lockdown group (aIRR = 1.42, 95% CI = 1.04-1.96; p = 0.028) compared to pre-COVID-19 lockdown period, adjusting for age, sex, employment status, household hunger, depression risk, and smoked substance use. DOT non-adherence was highest immediately following the initial lockdown (aIRR = 1.74, 95% CI = 1.17-2.67; p = 0.006). CONCLUSION: The COVID-19 lockdowns adversely effected adherence to TB DOT in the period after lockdowns were lifted. The change in DOT adherence persisted even after adjusting for socioeconomic and behavioral variables. We need a better understanding of what treatment adherence barriers were exacerbated by COVID-19 lockdowns to improve outcomes in post-pandemic times. TRIAL REGISTRATION: ClinicalTrials.gov Registration Number: NCT02840877. Registered on 19 July 2016.

Tuberculosis patients' satisfaction with directly observed treatment short course strategy and associated factors in Southern Ethiopia: a mixed method study.

BACKGROUND: Tuberculosis (TB) is a second major global public health problem and the leading infectious cause of death in Ethiopia. Patients under directly observed treatment short-courses (DOTs) have a higher treatment success rate and reduced drug resistance. A successful treatment outcome and adherence to the treatment are related to patient satisfaction with the DOT strategy. Client satisfaction is one of the indicators of the quality of care. In this perspective, there were limited studies in Ethiopia related to patient satisfaction with the DOTs strategy in the prevention and control of TB to achieve the ''END TB Strategy.'' Therefore, this study was aimed at identifying the TB patients' satisfaction with the DOTs strategy and associated factors in Gamo Zone, Southern Ethiopia. METHODS: An institutional-based cross-sectional study design for quantitative data and a phenomenological approach were employed for qualitative data. The calculated sample size was 374. A systematic random sampling method was used to select study participants. A pre-tested structured interviewer-administered questionnaire for quantitative data and focus group discussions (FGDs) for qualitative data were used for data collection. Bivariable and multivariable analyses were used. The determinants with a p-value < 0.05 were declared to have a significant association with the outcome variable, and an adjusted odd ratio with a 95% confidence interval (CI) was used. RESULTS: A total of 358 patients participated in the study, with a response rate of 95.72%. The majority of study participants' ages ranged between 25 and 34 years. The tuberculosis DOT satisfaction rate was 61.17% [56.10-66.25%, 95%CI]. The TB patients who took treatment for 20 weeks or more were 3.97 times [AOR = 3.97; 95% CI (1.55-10.16)] more likely to be satisfied with the DOTs service provided. However, the participants who perceived transport costs as high were 79% [AOR = 0.21; 95% CI (0.06-0.71)] less likely to be satisfied with DOTs. Qualitatively, the participants reported that there was a major problem with laboratory services, which resulted in delays and long appointments to get the results in addition to lack of clean toilets and safe water to swallow medications. CONCLUSION: The satisfaction rate for tuberculosis DOTs observed in this study appears to be relatively lower in comparison to other studies. Availing DOTs service nearby patients to enhance the accessibility of the service is crucial to improving patients' satisfaction with DOTs service. Reducing laboratory result delays by improving laboratory service is essential to enhancing patients' satisfaction with DOTs. Moreover, improving toilet services, and availing safe water to swallow medications is recommended to enhancing patients' satisfaction with DOTs service.

The introduction of video-enabled directly observed therapy (video-DOT) for patients with drug-resistant TB disease in Eswatini amid the COVID-19 pandemic - a retrospective cohort study.

BACKGROUND: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic. METHODS: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis. RESULTS: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis. CONCLUSIONS: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes.

A multi-centre randomised control trial of directly observed therapy to promote medication adherence in paediatric heart transplant recipients.

Medication non-adherence remains a significant challenge for adolescent heart transplant recipients. Building on the success of a pilot intervention study, herein we describe the protocol for a follow-up randomised control trial using mobile video directly observed therapy, featuring several innovations, to promote medication adherence in a multi-centre sample of adolescent heart transplant patients.

Prevalence of Extra-pulmonary Tuberculosis among Patients Diagnosed with Tuberculosis in a Tertiary Hospital in Bauchi, Northeastern Nigeria - A Five-Year Review.

BACKGROUND: Extra- pulmonary tuberculosis ( EPTB) contributes to the burden of Tuberculosis (TB) especially in developing countries. Despite this fact, information on the prevalence of EPTB is scarce. The aim of this study is to determine the five-year prevalence of EPTB among patients diagnosed with tuberculosis (TB) that attended and received treatment for TB at directly observed treatment short course (DOTS) clinic of Abubakar Tafawa Balewa University Teaching Hospital (ATBUTH), Bauchi, North-eastern Nigeria. METHODOLOGY: This is a retrospective review of all patients' records diagnosed with TB that attended and received treatment at the TB DOTS clinic of ATBUTH, Bauchi from January, 2017 to December, 2021. Extracted data was analyzed using IBM SPSS version 23.0 software. RESULT: There were 676 patients comprising of 389 (57.5%) males and 287 (42.5%) females and out of these, 208 had EPTB. The estimated five-year prevalence of EPTB in the studied cases was 30.8%. Tuberculosis of the spine was the predominant form of EPTB in this study with 117 (56.3%) cases. This was followed by TB Lymph nodes 40 (19.2%), TB Abdomen 36 (17.3%), TB Pleura 6 (2.9%), TB Pericardium 3 (1.4%), 2 (1.0%) each of TB Breast and CNS, and 1 (0.5%) each of TB Testicle and Upper arm. Seventy-eight (11.5%) patients were HIV positive, 549 (81.2%) were HIV-negative and the HIV status of 49 (7.2%) patients was unknown. CONCLUSION: The study showed prevalence of EPTB is still high as reported in some literature. Tuberculosis of spine was the commonest form of EPTB. These findings underscore the need for continued screening of EPTB to reduce the burden of TB in resource-poor countries.

CONTEXTE: La tuberculose extra-pulmonaire (TEP) contribue au fardeau de la tuberculose (TB), en particulier dans les pays en développement. Malgré ce fait, les informations sur la prévalence de la TEP sont rares. Le but de cette étude est de déterminer la prévalence sur cinq ans de la TEP chez les patients diagnostiqués avec la tuberculose (TB) qui ont fréquenté et reçu un traitement pour la TB au centre de traitement de courte durée sous observation directe (DOTS) de l'hôpital universitaire Abubakar Tafawa Balewa (ATBUTH), Bauchi, Nord-Est du Nigéria. MÉTHODOLOGIE: Il s'agit d'une revue rétrospective de tous les dossiers des patients diagnostiqués avec la TB qui ont fréquenté et reçu un traitement au centre de traitement DOTS de l'ATBUTH, Bauchi, de janvier 2017 à décembre 2021. Les données extraites ont été analysées à l'aide du logiciel IBM SPSS version 23.0. RÉSULTAT: Il y avait 676 patients comprenant 389 (57,5%) hommes et 287 (42,5%) femmes, dont 208 avaient une TEP. La prévalence estimée sur cinq ans de la TEP dans les cas étudiés était de 30,8%. La tuberculose de la colonne vertébrale était la forme prédominante de TEP dans cette étude avec 117 (56,3%) cas. Cela a été suivi par la TB des ganglions lymphatiques 40 (19,2%), la TB abdominale 36 (17,3%), la TB pleurale 6 (2,9%), la TB péricardique 3 (1,4%), 2 (1,0%) cas chacun de TB du sein et du SNC, et 1 (0,5%) cas chacun de TB testiculaire et du bras supérieur. Soixante-dix-huit (11,5%) patients étaient séropositifs, 549 (81,2%) étaient séronégatifs et le statut VIH de 49 (7,2%) patients était inconnu. CONCLUSION: L'étude a montré que la prévalence de la TEP est encore élevée, comme le rapporte certaines littératures. La tuberculose de la colonne vertébrale était la forme la plus courante de TEP. Ces résultats soulignent la nécessité de poursuivre le dépistage de la TEP pour réduire le fardeau de la TB dans les pays à ressources limitées. MOTS CLÉS: Tuberculose Extra-Pulmonaire, Prévalence, Bauchi, Nord-Est du Nigéria.

Estimated Costs of 4-Month Pulmonary Tuberculosis Treatment Regimen, United States.

We estimated direct costs of a 4-month or 6-month regimen for drug-susceptible pulmonary tuberculosis treatment in the United States. Costs were $23,000 per person treated. Actual treatment costs will vary depending on examination and medication charges, as well as expenses associated with directly observed therapy.

The Relationship Between Directly Observed Therapy for Chlamydia Infections and Retesting Rates in an Adolescent Population.

BACKGROUND: Chlamydia trachomatis is the most common reportable sexually transmitted infection in the United States, with >60% of reported cases occurring in individuals aged 15 to 24 years. US practice guidelines recommend directly observed therapy (DOT) for the treatment of chlamydia in adolescents, but almost no research has been done to evaluate whether DOT results in improved outcomes. METHODS: We conducted a retrospective cohort study of adolescents who sought care at 1 of 3 clinics within a large academic pediatric health system for a chlamydia infection. The study outcome was return for retesting within 6 months. Unadjusted analyses were performed using χ2 , Mann-Whitney U , and t tests, and adjusted analyses were performed using multivariable logistic regression. RESULTS: Of the 1970 individuals included in the analysis, 1660 (84.3%) received DOT and 310 (15.7%) had a prescription sent to a pharmacy. The population was primarily Black/African American (95.7%) and female (78.2%). After controlling for confounders, individuals who had a prescription sent to a pharmacy were 49% (95% confidence interval, 31%-62%) less likely than individuals who received DOT to return for retesting within 6 months. CONCLUSIONS: Despite clinical guidelines recommending the use of DOT for chlamydia treatment in adolescents, this is the first study to describe the association between DOT and an increase in the number of adolescents and young adults who return for sexually transmitted infection retesting within 6 months. Further research is needed to confirm this finding in diverse populations and explore nontraditional settings for the provision of DOT.

Recommendations for Use of Video Directly Observed Therapy During Tuberculosis Treatment - United States, 2023.

U.S. clinical practice guidelines recommend directly observed therapy (DOT) as the standard of care for tuberculosis (TB) treatment (1). DOT, during which a health care worker observes a patient ingesting the TB medications, has typically been conducted in person. Video DOT (vDOT) uses video-enabled devices to facilitate remote interactions between patients and health care workers to promote medication adherence and clinical monitoring. Published systematic reviews, a published meta-analysis, and a literature search through 2022 demonstrate that vDOT is associated with a higher proportion of medication doses being observed and similar proportions of cases with treatment completion and microbiologic resolution when compared with in-person DOT (2-5). Based on this evidence, CDC has updated the recommendation for DOT during TB treatment to include vDOT as an equivalent alternative to in-person DOT. vDOT can assist health department TB programs meet the U.S. standard of care for patients undergoing TB treatment, while using resources efficiently.

Randomized Controlled Trial of Automated Directly Observed Therapy for Measurement and Support of PrEP Adherence Among Young Men Who have Sex with Men.

Measurement of adherence to oral pre-exposure prophylaxis (PrEP) in real-time has been challenging. We developed DOT Diary, a smartphone application that combines automated directly observed therapy with a PrEP adherence visualization toolkit, and tested its ability to measure PrEP adherence and to increase adherence among a diverse cohort of young men who have sex with men (MSM). We enrolled 100 MSM in San Francisco and Atlanta and randomly assigned them 2:1 to DOT Diary versus standard of care. Concordance between DOT Diary measurement and drug levels in dried blood spots was substantial, with 91.0% and 85.3% concordance between DOT Diary and emtricitabine-triphosphate and tenofovir-diphosphate, respectively. There was no significant difference in the proportion of participants with detectable PrEP drug levels at 24 weeks between study arms. These results suggest DOT Diary is substantially better than self-reported measures of adherence, but additional interventions are needed to improve PrEP adherence over time.

RESUMEN: La medición de la adherencia a la profilaxis oral previa a la exposición (PrEP) en tiempo real ha constituido un desafío. Hemos desarrollado DOT Diary, una aplicación para teléfonos inteligentes que combina la terapia automatizada observada de forma directa con un kit de herramientas para visualizar la adherencia a la PrEP, y testeamos su capacidad para medir la adherencia a la PrEP, así como para aumentar la adherencia entre una cohorte variada de hombres jóvenes que tienen sexo con hombres (HSH). Reclutamos a 100 HSH en San Francisco y Atlanta y los asignamos aleatoriamente 2:1 a DOT Diary con respecto a la asistencia estándar. La concordancia entre la medición del DOT Diary y los niveles de fármacos en gotas de sangre seca fue sustancial, con un 91,0% y un 85,3% de concordancia entre el uso del DOT Diary y el de emtricitabina-trifosfato y tenofovir-difosfato, respectivamente. No hubo diferencias significativas en la proporción de participantes con niveles detectables del fármaco de la PrEP a las 24 semanas entre los brazos del estudio. Estos resultados sugieren que DOT Diary es sustancialmente superior a las medidas de adherencia que se notifican de forma personal, aunque hacen falta intervenciones adicionales para mejorar la adherencia a la PrEP a largo plazo.

Video directly observed therapy to improve adherence of human immunodeficiency virus infected adolescents to combination antiretroviral therapy: a proof-of-concept study.

Adherence to antiretroviral therapy (ART) is a major challenge for many youth living with HIV (YLWH). In this prospective proof-of-concept study, we assessed the feasibility and acceptability of conducting a study of video directly observed therapy (VDOT) as a method of improving medication adherence in YLWH who had a history of poor adherence to ART. The study had four phases; phase I - VDOT daily (4 months) using Facetime®; phase II - daily texting (2 months); phase III - weekly texting (3 months); phase IV - no intervention (3 months). Participants were seen in clinic on a monthly basis for assessment and laboratory evaluation. Five of eight eligible participants were enrolled. All achieved virologic suppression one month after enrollment. Three of five completed the study protocol and maintained virologic suppression through the 12-month period of study. Participant responses to the end-of-study questionnaire indicated satisfaction with the intervention and thought VDOT was helpful to them. Healthcare providers thought that the intervention was effective for some youth but was at times burdensome. This proof-of-concept study demonstrated that VDOT may be effective at improving medication adherence in previously poorly adherent YLWH and that larger studies of VDOT for such patients are both feasible and warranted.

Unregulated medication use and complications: a case study of prolonged self-treated tuberculosis in Nepal.

BACKGROUND: Tuberculosis (TB) is a global public health issue, particularly in resource-constrained countries like Nepal. This case report highlights the consequences of prolonged self-treatment and non-compliance with TB management protocols, emphasizing the need for increased awareness and intervention. CASE PRESENTATION: A 50-year-old male from Nepal self-medicated with anti-tubercular drugs for 13 years after completing the recommended course of treatment. He experienced worsening symptoms, including respiratory distress and visual impairment. Upon evaluation, he was diagnosed with chronic cavitary pulmonary aspergillosis. The patient received comprehensive treatment, including antifungal therapy, steroids, antibiotics, and respiratory support, resulting in significant improvement. CONCLUSIONS: This case highlights the dangers of self-treatment and non-compliance with TB management protocols. It emphasizes the importance of patient education, awareness programs, and regular follow-up to ensure treatment adherence and detect complications. The case also reveals gaps in the DOTS (Directly Observed Treatment, Short Course) program, including the need for improved surveillance, and a multidisciplinary approach. The ease of over-the-counter purchase of anti-tubercular drugs in Nepal contributed to the patient's prolonged self-medication, highlighting a concerning. The complications arising from prolonged self-medication underscore the need for increased awareness, intervention, and patient education in TB management. Improving patient education, raising awareness about the risks of self-medication, and integrating ophthalmologic evaluations into standard management are essential for better TB control in Nepal.

Barriers to tuberculosis treatment adherence in high-burden tuberculosis settings in Ashanti region, Ghana: a qualitative study from patient's perspective.

BACKGROUND: Despite having an effective community-based Directly Observed Therapy Short-course (DOTS) strategy for tuberculosis (TB) care, treatment adherence has been a major challenge in many developing countries including Ghana. Poor adherence results in discontinuity of treatment and leads to adverse treatment outcomes which pose an increased risk of drug resistance. This study explored barriers to TB treatment adherence and recommended potential patient-centered strategies to improve treatment adherence in two high-burden TB settings in the Ashanti region of Ghana. METHODS: The study was conducted among TB patients who defaulted on treatment in the Obuasi Municipal and Obuasi East districts in the Ashanti region. A qualitative phenomenology approach was used to explore the barriers to TB treatment adherence. Purposive sampling was adopted to select study participants with different sociodemographic backgrounds and experiences with TB care. Eligible participants were selected by reviewing the medical records of patients from health facility TB registers (2019-2021). Sixty-one (61) TB patients met the eligibility criteria and were contacted via phone call. Out of the 61 patients, 20 were successfully reached and consented to participate. In-depth interviews were conducted with participants using a semi-structured interview guide. All interviews were audio recorded and transcribed verbatim. The transcripts were imported into Atlas.ti version 8.4 software and analyzed using thematic content analysis. RESULTS: Food insecurity, cost of transportation to the treatment center, lack of family support, income insecurity, long distance to the treatment center, insufficient knowledge about TB, side effect of drugs, improvement in health after the intensive phase of the treatment regimen, and difficulty in accessing public transportation were the main co-occurring barriers to treatment adherence among the TB patients. CONCLUSION: The main barriers to TB treatment adherence identified in this study reveal major implementation gaps in the TB programme including gaps related to social support, food security, income security, knowledge, and proximity to treatment centers. Hence, to improve treatment adherence there is a need for the government and the National Tuberculosis Programme (NTP) to collaborate with different sectors to provide comprehensive health education, social and financial support as well as food aid to TB patients.

Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.