Background Targeted testing and treatment (TTT) for latent tuberculosis infection (LTBI) is a recommended strategy to accelerate TB reductions and further tuberculosis elimination in the United States (US). Evidence on cost-effectiveness of TTT for key populations can help advance this goal. Methods We used a model of TB transmission to estimate the numbers of individuals who could be tested by interferon-γ release assay (IGRA) and treated for LTBI with three months of self-administered rifapentine and isoniazid (3HP) under various TTT scenarios. Specifically, we considered rapidly scaling up TTT among people who are non-US-born, diabetic, HIV-positive, homeless or incarcerated in California, Florida, New York, and Texas – states where more than half of US TB cases occur. We projected costs (from the healthcare system perspective, in 2018 dollars), thirty-year reductions in TB incidence, and incremental cost effectiveness (cost per quality-adjusted life year [QALY] gained) for TTT in each modeled population. Results The projected cost effectiveness of TTT differed substantially by state and population, while the health impact (number of TB cases averted) was consistently greatest among the non-US-born. TTT was most cost-effective among persons living with HIV (from $2,828/QALY gained in Florida to $11,265/QALY gained in New York) and least cost-effective among people with diabetes (from $223,041/QALY gained in California to $817,753 /QALY in New York). Conclusions The modeled cost-effectiveness of TTT for LTBI varies across states but was consistently greatest among people living with HIV, moderate among people who are non-US-born, incarcerated, or homeless, and least cost-effective among people living with diabetes.

Background Failing to account for the resources required to successfully implement public health interventions can lead to an underestimation of costs and budget impact, optimistic cost-effectiveness estimates, and ultimately a disconnect between published evidence and public health decision-making. Methods We developed a conceptual framework for assessing implementation costs. We illustrate the use of this framework with case studies involving interventions for tuberculosis and HIV/AIDS in resource-limited settings. Results Costs of implementing public health interventions may be conceptualized as occurring across three phases: design, initiation, and maintenance. In the design phase, activities include developing intervention components and establishing necessary infrastructure (e.g., technology, standard operating procedures). Initiation phase activities include training, initiation of supply chains and quality assurance procedures, and installation of equipment. Implementation costs in the maintenance phase include ongoing technical support, monitoring and evaluation, and troubleshooting unexpected obstacles. Within each phase, implementation costs can be incurred at the site of delivery (“site-specific” costs) or more centrally (“above-service” or “central” costs). For interventions evaluated in the context of research studies, implementation costs should be classified as programmatic, research-related, or shared research/program costs. Purely research-related costs are often excluded from analysis of programmatic implementation. Conclusions In evaluating public health interventions in resource-limited settings, accounting for implementation costs enables more realistic estimates of budget impact and cost-effectiveness and provides important insights into program feasibility, scale-up, and sustainability. Assessment of implementation costs should be planned prospectively and performed in a standardized manner to ensure generalizability.

OBJECTIVE:Dengue is a worldwide public health problem with approximately 50 million cases reported annually. The World Health Organization proposed a revised classification system in 2008 to more effectively identify the patients who are at increased risk of complications from dengue. Few studies have validated this new classification system in clinical practice. We conducted a cross-sectional study of patients hospitalized for dengue in Dourados, Mato Grosso do Sul, Brazil, to evaluate the capacity of the two classification systems for detecting severe cases of dengue.MATERIALS AND METHODS:We conducted a cross-sectional study of survey data from the medical records of patients admitted to the University Hospital of the Federal University of Grande Dourados under clinical suspicion of dengue during an epidemic from September 2009 to April 2010.RESULTS:The distribution of patients according to the traditional classification system was as follows: dengue fever, 150/181 (82.9%); dengue hemorrhagic fever, 27/181 (14.9%); and dengue hemorrhagic shock, 4/181 (2.2%). Using the revised classification system, the distribution was as follows: dengue without warning signs, 45/181 (24.3%); dengue with warning signs, 107/181 (59.1%); and severe dengue, 29/181 (15.6%). Of the 150 patients classified as having dengue fever, 105 (70%) were reclassified as having dengue with warning signs or severe dengue.CONCLUSION:These data demonstrate that the revised classification system has greater discriminatory power for detecting patients at risk of progression to severe disease and those needing hospitalization.

Background While household contact investigation is widely recommended as a means to reduce the burden of tuberculosis (TB) among children, only 27% of eligible pediatric household contacts globally received preventive treatment in 2018. We assessed the cost-effectiveness of household contact investigation for TB treatment and short-course preventive therapy provision for children under 15 years old across 12 high TB burden countries. Methods We used decision analysis to compare the costs and estimated effectiveness of three intervention scenarios: (a) status quo (existing levels of coverage with isoniazid preventive therapy), (b) contact investigation with treatment of active TB but no additional preventive therapy, and (c) contact investigation with TB treatment and provision of short-course preventive therapy. Using country-specific demographic, epidemiological and cost data from the literature, we estimated annual costs (in 2018 USD) and the number of TB cases and deaths averted across 12 countries. Incremental cost effectiveness ratios were assessed as cost per death and per disability-adjusted life year [DALY] averted. Findings Our model estimates that contact investigation with treatment of active TB and provision of preventive therapy could be highly cost-effective compared to the status quo (ranging from $100 per DALY averted in Malawi to $1,600 in Brazil; weighted average $383 per DALY averted [uncertainty range: $248 – $1,130]) and preferred to contact investigation without preventive therapy (weighted average $751 per DALY averted [uncertainty range: $250 – $1,306]). Key drivers of cost-effectiveness were TB prevalence, sensitivity of TB diagnosis, case fatality for untreated TB, and cost of household screening. Interpretation Based on this modeling analysis of available published data, household contact investigation with provision of short-course preventive therapy for TB has a value-for-money profile that compares favorably with other interventions. Funding Unitaid (2017–20-IMPAACT4TB).

No abstract

In rapidly growing, high burden urban centers, identifying tuberculosis (TB) transmission hotspots and understanding potential impact of interventions can inform future control and prevention strategies.Using data on local demography, TB reports, and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e. "hotspots") in DSCC and DNCC. We developed ward-level transmission models and estimated the potential epidemiological impact of three TB interventions: active case finding (ACF), mass preventive therapy (PT), and a combination of ACF and PT, implemented either citywide or targeted to high-incidence hotspots. There was substantial geographic heterogeneity in the estimated TB incidence in both DSCC and DNCC: incidence in the highest-incidence wards was over ten times higher than in the lowest-incidence wards in each city corporation. ACF, PT and combined ACF plus PT delivered to 10% of the population reduced TB incidence by a projected 7-9%, 13-15%, and 19-23% over five years, respectively. Targeting TB hotspots increased the projected reduction in TB incidence achieved by each intervention 1.4-to 1.8-fold. The geographical pattern of TB notifications suggests high levels of ongoing TB transmission in DSCC and DNCC, with substantial heterogeneity at the ward level. Interventions that reduce transmission are likely to be highly effective and incorporating notification data at the local level can further improve intervention efficiency.

To study whether treatment with the beta-blocker atenolol (AT) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rats were treated with AT (1.5 mg · kg(-1), intravenously) or saline solution (SS) prior to I (60 minutes), which was produced by occlusion of the superior mesenteric artery, and/or R (120 minutes). After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy analysis. Compared to the sham group, jejunal contractions were similar in the I + AT and the I/R + AT groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the I + AT and the I/R + AT. These results suggest that AT may attenuate intestinal dysfunction caused by I and I/R.

Background: In rapidly growing, high burden urban centers, identifying tuberculosis (TB) transmission hotspots and understanding potential impact of interventions can inform future control and prevention strategies. Methods: Using data on local demography, TB reports, and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e. hotspot) in DSCC and DNCC. We developed ward-level transmission models and estimated the potential epidemiological impact of three TB interventions: active case finding (ACF), mass preventive therapy (PT), and a combination of ACF and PT, implemented either citywide or targeted to high-incidence hotspots. Results: There was substantial geographic heterogeneity in the estimated TB incidence in both DSCC and DNCC: incidence in the highest-incidence wards was over ten times higher than in the lowest-incidence wards in each city corporation. ACF, PT and combined ACF plus PT delivered to 10% of the population reduced TB incidence by a projected 7-9%, 13-15%, and 19-23% over five years, respectively. Targeting TB hotspots increased the projected reduction in TB incidence achieved by each intervention 1.4- to 1.8-fold. Conclusions: The geographical pattern of TB notifications suggests high levels of ongoing TB transmission in DSCC and DNCC, with substantial heterogeneity at the ward level. Interventions that reduce transmission are likely to be highly effective, and incorporating notification data at the local level can further improve intervention efficiency.