Optimal Use of New and Existing Drugs for Tuberculosis Control

Tuberculosis (TB) recently surpassed HIV as the world’s leading infectious killer. Because antibiotic therapy forms the cornerstone of TB control, prevention, and treatment, it is important to apply TB drugs in a way that maximizes their potential benefits while minimizing the risks of resistance. Here, I present three modeling analyses intended to explore these tensions inherent in the use of TB drugs. Preventive therapy involves the use of antimicrobials in asymptomatic and noninfectious individuals, and has been applied to diseases ranging from TB to HIV to malaria. In my first paper, I outline how population use of preventive therapy could increase, decrease, or have non-monotonic effects on the prevalence of drug resistance, depending on the relative contributions of resistance acquired as a result of preventive therapy, resistance acquired as a result of treatment for active disease, and transmitted resistance. In my second paper, I consider the specific use of isoniazid preventive therapy (IPT) to prevent active TB among people living with HIV. Previous models have suggested that widespread IPT use could increase the prevalence of drug resistant TB by providing a selective pressure in favor of resistant strains. In this paper, I show that the impact of IPT on drug resistance is highly dependent on the projected TB/HIV epidemic trends, and that the risks of resistance are likely to remain low for even lifelong IPT durations as long as transmission is already declining. Finally, in my third paper, I present a decision analytic model to determine the optimal targeting of the new TB drug bedaquiline for patients with pre-existing resistance to other available drugs. The optimal use strategy for this new drug depends on the outcome being considered; whereas more liberal strategies would likely decrease resistance to existing drugs as well as onward transmission, more restrictive strategies would decrease resistance to bedaquiline. More research is needed to confirm that more liberal bedaquiline use strategies would improve life expectancy. Overall, these papers illustrate the complexity of the decisions surrounding optimal TB drug use. Thoughtful antibiotic policies, coupled with continued innovation, are needed to effectively combat the global burden of TB

GenerAges : Generations as They Age

GenerAges examines the history and culture of the 20th century that shaped the lives of Americans age 65 and older today, with a special focus on the generations coming of age in the 1920s (centenarians), ‘40s (the Greatest Generation) and ‘60s (Age of Aquarius). The lengthy work is full of statistics and information regarding what was then the technological revolution of the early 20th century as well as the cultural revolution of the 1960s and early 1970s that ushered in a new era of civil rights and women’s liberation and equality. While this study emphasizes the enormous amount of technological, social and cultural change over the past century, it also stresses a certain commonality found among generations in their quest for peace and prosperity, and that “each will be on the cutting edge of fashion, technology and modern conveniences; and each will recede into history with relative rapidity, appearing amusingly antiquated in the process.

Defining County-Level Terrestrial Rabies Freedom Using the US National Rabies Surveillance System: Surveillance Data Analysis

Background: Rabies is a deadly zoonotic disease with nearly 100% fatality rate. In the United States, rabies virus persists in wildlife reservoirs, with occasional spillover into humans and domestic animals. The distribution of reservoir hosts in US counties plays an important role in public health decision-making, including the recommendation of lifesaving postexposure prophylaxis upon suspected rabies exposures. Furthermore, in surveillance data, it is difficult to discern whether counties have no cases reported because rabies was not present or because counties have an unreported rabies presence. These epizootics are monitored by the National Rabies Surveillance System (NRSS), to which approximately 130 state public health, agriculture, and academic laboratories report animal rabies testing statistics. Historically, the NRSS classifies US counties as free from terrestrial rabies if, over the previous 5 years, they and any adjacent counties did not report any rabies cases and they tested ≥15 reservoir animals or 30 domestic animals. Objective: This study aimed to describe and evaluate the historical NRSS rabies-free county definition, review possibilities for improving this definition, and develop a model to achieve more precise estimates of the probability of terrestrial rabies freedom and the number of reported county-level terrestrial rabies cases. Methods: Data submitted to the NRSS by state and territorial public health departments and the US Department of Agriculture Wildlife Services were analyzed to evaluate the historical rabies-free definition. A zero-inflated negative binomial model created county-level predictions of the probability of rabies freedom and the expected number of rabies cases reported. Data analyzed were from all animals submitted for laboratory diagnosis of rabies in the United States from 1995 to 2020 in skunk and raccoon reservoir territories, excluding bats and bat variants. Results: We analyzed data from 14,642 and 30,120 county-years in the raccoon and skunk reservoir territories, respectively. Only 0.85% (9/1065) raccoon county-years and 0.79% (27/3411) skunk county-years that met the historical rabies-free criteria reported a case in the following year (99.2% negative predictive value for each), of which 2 were attributed to unreported bat variants. County-level model predictions displayed excellent discrimination for detecting zero cases and good estimates of reported cases in the following year. Counties classified as rabies free rarely (36/4476, 0.8%) detected cases in the following year. Conclusions: This study concludes that the historical rabies freedom definition is a reasonable approach for identifying counties that are truly free from terrestrial raccoon and skunk rabies virus transmission. Gradations of risk can be measured using the rabies prediction model presented in this study. However, even counties with a high probability of rabies freedom should maintain rabies testing capacity, as there are numerous examples of translocations of rabies-infected animals that can cause major changes in the epidemiology of rabies

Assessment of a health facility based active case finding system for Ebola virus disease in Mbandaka, Democratic Republic of the Congo, June-July 2018.

BACKGROUND: The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system's implementation. METHODS: From 23 June - 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs' awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff's awareness of EVD. RESULTS: ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses. CONCLUSION: HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing

Newlywed Reports of Social Support During Engagement: What Worked and What Failed

This study investigated newlywed reports of social support during the engagement period via qualitative, in-depth interviews with 36 recently married heterosexual couples (N ¼ 72 total interviews). Specifically, the study examined what worked and what failed in the social support process for engaged couples. Overall, results revealed that helpful support is generally more plentiful during the engagement period than unhelpful support, and emotional support is the most prevalent of the various types of social support. The most common providers of social support to engaged individuals were family members and friends. Finally, the study revealed that most people felt a sense of perceived support in their social networks if they were in need of it at any point during their engagements. Keywords: Engagement; Interpersonal Communication; Marriage; Social Support The period of engagement is a significant stage of life for many couples. As a couple prepares for their upcoming marriage, they will likely experience multiple changes. These can include a physical move, adjustments in the management of finances, adaptation to and inclusion of additional family members (i.e., in-laws), and reassignments of regular household duties. Additionally, there are emotional changes Amber S. Messersmit

Newlywed Reports of Social Support During Engagement: What Worked and What Failed

This study investigated newlywed reports of social support during the engagement period via qualitative, in-depth interviews with 36 recently married heterosexual couples (N = 72 total interviews). Specifically, the study examined what worked and what failed in the social support process for engaged couples. Overall, results revealed that helpful support is generally more plentiful during the engagement period than unhelpful support, and emotional support is the most prevalent of the various types of social support. The most common providers of social support to engaged individuals were family members and friends. Finally, the study revealed that most people felt a sense of perceived support in their social networks if they were in need of it at any point during their engagements

How could preventive therapy affect the prevalence of drug resistance? Causes and consequences

Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects

Optimal Distribution of Medical Backpacks and Health Surveillance Assistants in Malawi

Despite recent progress, Malawi continues to perform poorly on key health indicators such as child mortality and life expectancy. These problems are exacerbated by a severe lack of access to health care. Health Surveillance Assistants (HSAs) help bridge this gap by providing community-level access to basic health care services. However, the success of these HSAs is limited by a lack of supplies and long distances between HSAs and patients. To address this issue, we used large-scale p-median and capacitated facility location problems to create a scalable, three-tiered plan for optimal allocation of HSAs, HSA designated medical backpacks, and backpack resupply centers. Our analysis uses real data on the location and characteristics of hospitals, health centers, and the general population. In addition to offering specific recommendations for HSA, backpack, and resupply center locations, it provides general insights into the scope of the proposed HSA backpack program scale-up. In particular, it demonstrates the importance of local health centers to the resupply network. The proposed assignments are robust to changes in the underlying population structure, and could significantly improve access to medical supplies for both HSAs and patients