Effectiveness of UNAIDS targets and HIV vaccination across 127 countries.

The HIV pandemic continues to impose enormous morbidity, mortality, and economic burdens across the globe. Simultaneously, innovations in antiretroviral therapy, diagnostic approaches, and vaccine development are providing novel tools for treatment-as-prevention and prophylaxis. We developed a mathematical model to evaluate the added benefit of an HIV vaccine in the context of goals to increase rates of diagnosis, treatment, and viral suppression in 127 countries. Under status quo interventions, we predict a median of 49 million [first and third quartiles 44M, 58M] incident cases globally from 2015 to 2035. Achieving the Joint United Nations Program on HIV/AIDS 95-95-95 target was estimated to avert 25 million [20M, 33M] of these new infections, and an additional 6.3 million [4.8M, 8.7M] reduction was projected with the 2020 introduction of a 50%-efficacy vaccine gradually scaled up to 70% coverage. This added benefit of prevention through vaccination motivates imminent and ongoing clinical trials of viable candidates to realize the goal of HIV control.

National- and state-level impact and cost-effectiveness of nonavalent HPV vaccination in the United States.

Every year in the United States more than 12,000 women are diagnosed with cervical cancer, a disease principally caused by human papillomavirus (HPV). Bivalent and quadrivalent HPV vaccines protect against 66% of HPV-associated cervical cancers, and a new nonavalent vaccine protects against an additional 15% of cervical cancers. However, vaccination policy varies across states, and migration between states interdependently dilutes state-specific vaccination policies. To quantify the economic and epidemiological impacts of switching to the nonavalent vaccine both for individual states and for the nation as a whole, we developed a model of HPV transmission and cervical cancer incidence that incorporates state-specific demographic dynamics, sexual behavior, and migratory patterns. At the national level, the nonavalent vaccine was shown to be cost-effective compared with the bivalent and quadrivalent vaccines at any coverage despite the greater per-dose cost of the new vaccine. Furthermore, the nonavalent vaccine remains cost-effective with up to an additional 40% coverage of the adolescent population, representing 80% of girls and 62% of boys. We find that expansion of coverage would have the greatest health impact in states with the lowest coverage because of the decreasing marginal returns of herd immunity. Our results show that if policies promoting nonavalent vaccine implementation and expansion of coverage are coordinated across multiple states, all states benefit both in health and in economic terms.

Dynamic Models of Infectious Disease Transmission in Prisons and the General Population.

Incarcerated populations experience elevated burdens of infectious diseases, which are exacerbated by limited access to prevention measures. Dynamic models are used to assess the spread and control of diseases within correctional facilities and repercussions on the general population. Our systematic review of dynamic models of infectious diseases within correctional settings identified 34 studies published between 1996 and 2017. Of these, 23 focused on disease dynamics and intervention in prison without accounting for subsequent spread to the community. The main diseases modeled in these studies were human immunodeficiency virus (HIV; n = 14, 41%), tuberculosis (TB; n = 10, 29%), and hepatitis C virus (HCV; n = 7, 21%). Models were fitted to epidemiologic data in 14 studies; uncertainty and sensitivity analyses were conducted in 8, and validation of model projection against empirical data was done in 1 study. According to the models, prison-based screening and treatment may be highly effective strategies for reducing the burden of HIV, TB, HCV, and other sexually transmissible infections among prisoners and the general community. Decreasing incarceration rates were projected to reduce HIV and HCV infections among people who inject drugs and TB infections among all prisoners. Limitations of the modeling studies and opportunities for using dynamic models to develop quantitative evidence for informing prison infection control measures are discussed.

Treatments of Missing Values in Large National Data Affect Conclusions: The Impact of Multiple Imputation on Arthroplasty Research.

BACKGROUND: Despite the advantages of large, national datasets, one continuing concern is missing data values. Complete case analysis, where only cases with complete data are analyzed, is commonly used rather than more statistically rigorous approaches such as multiple imputation. This study characterizes the potential selection bias introduced using complete case analysis and compares the results of common regressions using both techniques following unicompartmental knee arthroplasty. METHODS: Patients undergoing unicompartmental knee arthroplasty were extracted from the 2005 to 2015 National Surgical Quality Improvement Program. As examples, the demographics of patients with and without missing preoperative albumin and hematocrit values were compared. Missing data were then treated with both complete case analysis and multiple imputation (an approach that reproduces the variation and associations that would have been present in a full dataset) and the conclusions of common regressions for adverse outcomes were compared. RESULTS: A total of 6117 patients were included, of which 56.7% were missing at least one value. Younger, female, and healthier patients were more likely to have missing preoperative albumin and hematocrit values. The use of complete case analysis removed 3467 patients from the study in comparison with multiple imputation which included all 6117 patients. The 2 methods of handling missing values led to differing associations of low preoperative laboratory values with commonly studied adverse outcomes. CONCLUSION: The use of complete case analysis can introduce selection bias and may lead to different conclusions in comparison with the statistically rigorous multiple imputation approach. Joint surgeons should consider the methods of handling missing values when interpreting arthroplasty research.

Bolstering Community Cooperation in Ebola Resurgence Protocols: Combining Field Blood Draw and Point-of-Care Diagnosis.

Alison Galvani and colleagues describe a community-based protocol to improve cooperation with Ebola testing as well as contact tracing, quarantining, and treatment.

The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States.

BACKGROUND: The effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs). METHODS: To evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040. RESULTS: Increasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%. CONCLUSIONS: Interferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States.

Effect of Ebola progression on transmission and control in Liberia.

BACKGROUND: The Ebola outbreak that is sweeping across West Africa is the largest, most volatile, and deadliest Ebola epidemic ever recorded. Liberia is the most profoundly affected country, with more than 3500 infections and 2000 deaths recorded in the past 3 months. OBJECTIVE: To evaluate the contribution of disease progression and case fatality on transmission and to examine the potential for targeted interventions to eliminate the disease. DESIGN: Stochastic transmission model that integrates epidemiologic and clinical data on incidence and case fatality, daily viral load among survivors and nonsurvivors evaluated on the basis of the 2000-2001 outbreak in Uganda, and primary data on contacts of patients with Ebola in Liberia. SETTING: Montserrado County, Liberia, July to September 2014. MEASUREMENTS: Ebola incidence and case-fatality records from 2014 Liberian Ministry of Health and Social Welfare. RESULTS: The average number of secondary infections generated throughout the entire infectious period of a single infected case, R, was estimated as 1.73 (95% CI, 1.66 to 1.83). There was substantial stratification between survivors (RSurvivors), for whom the estimate was 0.66 (CI, 0.10 to 1.69), and nonsurvivors (RNonsurvivors), for whom the estimate was 2.36 (CI, 1.72 to 2.80). The nonsurvivors had the highest risk for transmitting the virus later in the course of disease progression. Consequently, the isolation of 75% of infected individuals in critical condition within 4 days from symptom onset has a high chance of eliminating the disease. LIMITATION: Projections are based on the initial dynamics of the epidemic, which may change as the outbreak and interventions evolve. CONCLUSION: These results underscore the importance of isolating the most severely ill patients with Ebola within the first few days of their symptomatic phase. PRIMARY FUNDING SOURCE: National Institutes of Health.

Examining County-Level Associations between Federally Qualified Health Centers and Sexually Transmitted Infections: A Political Ecology of Health Framework.

Federally Qualified Health Centers (FQHCs) are the largest providers of healthcare for sexually transmitted infections (STIs) in medically underserved communities in the United States (US). Through the Affordable Care Act (ACA), FQHCs have grown in number, but the impact of this growth on STIs is poorly understood. This ecological study seeks to quantify the association between FQHCs and STI prevalence in all US counties. Variables were described utilizing medians and interquartile ranges, and distributions were compared using Kruskal-Wallis tests. Median rates of chlamydia in counties with high, low, and no FQHCs were 370.3, 422.6, and 242.1 cases per 100,000 population, respectively. Gonorrhea rates were 101.9, 119.7, and 49.9 cases per 100,000 population, respectively. Multivariable linear regression models, adjusted for structural and place-based characteristics (i.e., Medicaid expansion, social vulnerability, metropolitan status, and region), were used to examine county-level associations between FQHCs and STIs. Compared to counties with no FQHCs, counties with a high number of FQHCs had chlamydia rates that were an average of 68.6 per 100,000 population higher (ß = 68.6, 95% CI: 45.0, 92.3) and gonorrhea rates that were an average of 25.2 per 100,000 population higher (ß = 25.2, 95% CI: 13.2, 37.2). When controlled for salient factors associated with STI risks, greater FQHC availability was associated with greater diagnosis and treatment of STIs. These findings provide empirical support for the utility of a political ecology of health framework and the critical role of FQHCs in confronting the STI epidemic in the US.

Barriers to conducting independent quantitative research in low-income countries: A cross-sectional study of public health graduate students in Liberia.

INTRODUCTION: During recent disease outbreaks, quantitative research has been used to investigate intervention scenarios while accounting for local epidemiological, social, and clinical context. Despite the value of such work, few documented research efforts have been observed to originate from low-income countries. This study aimed to assess barriers that may be limiting the awareness and conduct of quantitative research among Liberian public health graduate students. METHODS: A semi-structured questionnaire was administered September-November 2021 to Master's in Public Health (MPH) students in Liberia. Potential barriers around technology access, understanding of quantitative science, and availability of mentorship were interrogated. Associations between barriers and self-reported likelihood of conducting quantitative research within six months of the investigation period were evaluated using ordinal logistic regression. RESULTS: Among 120 participating MPH students, 86% reported owning a personal computer, but 18.4% and 39.4% had machines with malfunctioning hardware and/or with battery power lasting ≤2 hours, respectively. On average, students reported having poor internet network 3.4 days weekly. 47% reported never using any computer software for analysis, and 46% reported no specific knowledge on statistical analysis. Students indicated spending a median 30 minutes per week reading scientific articles. Moreover, 50% had no access to quantitative research mentors. Despite barriers, 59% indicated they were very likely to undertake quantitative research in the next 6 months; only 7% indicated they were not at all likely. Computer ownership was found to be statistically significantly associated with higher likelihood of conducting quantitative research in the multivariable analysis (aOR: 4.90,95% CI: 1.54-16.3). CONCLUSION: The high likelihood of conducting quantitative research among MPH students contrasts with limitations around computing capacity, awareness of research tools/methods, and access to mentorship. To promote rigorous analytical research in Liberia, there is a need for systematic measures to enhance capacity for diverse quantitative methods through efforts sensitive to the local research environment.

Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016-2019.

Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The "Treat all" strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 -December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30-45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8-51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21-2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51-3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35-44 (aHR 0.65, 95%CI: 0.44-0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39-0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53-3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75-3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57-6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51-0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20-0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects-average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06-1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11-2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01-0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004-0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes.

Potential Impacts of Mass Nutritional Supplementation on Measles Dynamics: A Simulation Study.

The bidirectional interaction between undernutrition and infection can be devastating to child health. Nutritional deficiencies impair immunity and increase susceptibility to infection. Simultaneously, infections compound undernutrition by increasing metabolic demand and impairing nutrient absorption. Treatment of acute malnutrition (wasting) can reverse some of its deleterious effects and reduce susceptibility to infectious diseases. Nutrition-specific approaches may be packaged with other interventions, including immunization, to support overall child health. To understand how mass nutritional supplementation, treatment of wasting, and vaccination affect the dynamics of a vaccine-preventable infection, we developed a population-level, compartmental model of measles transmission stratified by age and nutrition status. We simulated a range of scenarios to assess the potential reductions in measles infection and mortality associated with targeted therapeutic feeding for children who are wasted and with a mass supplementation intervention. Nutrition interventions were assumed to increase engagement with the health sector, leading to increased vaccination rates. We found that the combination of wasting treatment and mass supplementation coverage followed by an increase in vaccination coverage of non-wasted children from a baseline of 75% to 85%, leads to 34% to 57% and 65% to 77% reduction in measles infection and mortality and 56% to 60% reduction in overall mortality among wasted children, compared with the wasting treatment alone. Our work highlights the synergistic benefits that may be achieved by leveraging mass nutritional supplementation as a touch point with the health system to increase rates of vaccination and improve child survival beyond what would be expected from the additive benefits of each intervention.

Data-driven analyses of behavioral strategies to eliminate cysticercosis in sub-Saharan Africa.

BACKGROUND: The multi-host taeniosis/cysticercosis disease system is associated with significant neurological morbidity, as well as economic burden, globally. We investigated whether lower cost behavioral interventions are sufficient for local elimination of human cysticercosis in Boulkiemdé, Sanguié, and Nayala provinces of Burkina Faso. METHODOLOGY/PRINCIPAL FINDINGS: Province-specific data on human behaviors (i.e., latrine use and pork consumption) and serological prevalence of human and pig disease were used to inform a deterministic, compartmental model of the taeniosis/cysticercosis disease system. Parameters estimated via Bayesian melding provided posterior distributions for comparing transmission rates associated with human ingestion of Taenia solium cysticerci due to undercooking and human exposure to T. solium eggs in the environment. Reductions in transmission via these pathways were modeled to determine required effectiveness of a market-focused cooking behavior intervention and a community-led sanitation and hygiene program, independently and in combination, for eliminating human cysticercosis as a public health problem (<1 case per 1000 population). Transmission of cysticerci due to consumption of undercooked pork was found to vary significantly across transmission settings. In Sanguié, the rate of transmission due to undercooking was 6% higher than that in Boulkiemdé (95% CI: 1.03, 1.09; p-value < 0.001) and 35% lower than that in Nayala (95% CI: 0.64, 0.66; p-value < 0.001). We found that 67% and 62% reductions in undercooking of pork consumed in markets were associated with elimination of cysticercosis in Nayala and Sanguié, respectively. Elimination of active cysticercosis in Boulkiemdé required a 73% reduction. Less aggressive reductions of 25% to 30% in human exposure to Taenia solium eggs through sanitation and hygiene programs were associated with elimination in the provinces. CONCLUSIONS/SIGNIFICANCE: Despite heterogeneity in effectiveness due to local transmission dynamics and behaviors, education on the importance of proper cooking, in combination with community-led sanitation and hygiene efforts, has implications for reducing morbidity due to cysticercosis and neurocysticercosis.

Coordinated support for local action: Modeling strategies to facilitate behavior adoption in urban-poor communities of Liberia for sustained COVID-19 suppression.

BACKGROUND: Long-term suppression of SARS-CoV-2 transmission will involve strategies that recognize the heterogeneous capacity of communities to undertake public health recommendations. We highlight the epidemiological impact of barriers to adoption and the potential role of community-led coordination of support for cases and high-risk contacts in urban slums. METHODS: A compartmental model representing transmission of SARS-CoV-2 in urban poor versus less socioeconomically vulnerable subpopulations was developed for Montserrado County, Liberia. Adoption of home-isolation behavior was assumed to be related to the proportion of each subpopulation residing in housing units with multiple rooms and with access to sanitation, water, and food. We evaluated the potential impact of increasing the maximum attainable proportion of adoption among urban poor following the scheduled lifting of the state of emergency. RESULTS: Without intervention, the model estimated higher overall infection burden but fewer severe cases among urban poor versus the less socioeconomically vulnerable population. With self-isolation by mildly symptomatic individuals, median reductions in cumulative infections, severe cases, and maximum daily incidence were 7.6% (IQR: 2.2%-20.9%), 7.0% (2.0%-18.5%), and 9.9% (2.5%-31.4%), respectively, in the urban poor subpopulation and 16.8% (5.5%-29.3%), 15.0% (5.0%-26.4%), and 28.1% (9.3%-47.8%) in the less socioeconomically vulnerable population. An increase in the maximum attainable percentage of behavior adoption by the urban slum subpopulation was associated with median reductions of 19.2% (10.1%-34.0%), 21.1% (13.3%-34.2%), and 26.0% (11.5%-48.9%) relative to the status quo scenario. CONCLUSIONS: Post-lockdown recommendations that prioritize home-isolation by confirmed cases are limited by resource constraints. Investing in community-based initiatives that coordinate support for self-identified cases and their contacts could more effectively suppress COVID-19 in settings with socioeconomic vulnerabilities.

Interruption of tuberculosis detection and care during the Ebola virus disease epidemic (2014-2015) in Liberia: time-series analyses for 2013-2017.

OBJECTIVE: Interrupted time-series analyses, using 5 years of routinely collected health information system data, were conducted to estimate the magnitude of impact of the 2014-2015 Ebola virus disease (EVD) epidemic and determine trends in tuberculosis (TB) care services in Liberia. METHODS: A segmented linear regression model was used to generate estimates and predictions for trends for three TB service indicators before, during, and after EVD, from January 2013 to December 2017. RESULTS: It was found that the number of presumptive TB cases declined significantly at the start of the EVD outbreak, with an estimated loss of 3222 cases (95% confidence interval (CI) -5691 to -752; P = 0.014). There was also an estimated loss of 709 cases per quarter post-EVD (95% CI -1346 to -71; P = 0.032). However, over the post-EVD period, quarterly increases were observed in the proportion of smear-positive to presumptive cases (1.45%, 95% CI 0.38% to 2.5%; P = 0.011) and the proportion of treatment success to TB cases evaluated (3.3%, 95% CI 0.82% to 5.79%; P = 0.013). CONCLUSIONS: These findings suggest that the EVD outbreak (2014-2015) negatively affected TB care services. Rigorous quantitative analyses can be used to assess the magnitude of interruption and advocate for preparedness in settings with limited healthcare capacity.

Participatory Design and Process Testing to Optimize Utility, Usability, and Acceptability of a Mobile Game for Promoting Evidence-Driven Public Health Decision-Making in Resource-Constrained Settings.

Innovative game-based training methods that leverage the ubiquity of cellphones and familiarity with phone-based interfaces have the potential to transform the training of public health practitioners in low-income countries such as Liberia. This article describes the design, development, and testing of a prototype of the Figure It Out mobile game. The prototype game uses a disease outbreak scenario to promote evidence-based decision-making in determining the causative agent and prescribing intervention measures to minimize epidemiological and logistical burdens in resource-limited settings. An initial prototype of the game developed by the US team was playtested and evaluated by focus groups with 20 University of Liberia Masters of Public Health (UL MPH) students. Results demonstrate that the learning objectives-improving search skills for identifying scientific evidence and considering evidence before decision-making during a public health emergency-were considered relevant and important in a setting that has repeatedly and recently experienced severe threats to public health. However, some of the game mechanics that were thought to enhance engagement such as trial-and-error and choose-your-own-path gameplay, were perceived by the target audience as distracting or too time-consuming, particularly in the context of a realistic emergency scenario. Gameplay metrics that mimicked real-world situations around lives lost, money spent, and time constraints during public health outbreaks were identified as relatable and necessary considerations. Our findings reflect cultural differences between the game development team and end users that have emphasized the need for end users to have an integral part of the design team; this formative evaluation has critically informed next steps in the iterative development process. Our multidisciplinary, cross-cultural and cross-national design team will be guided by Liberia-based public health students and faculty, as well as community members who represent our end user population in terms of experience and needs. These stakeholders will make key decisions regarding game objectives and mechanics, to be vetted and implemented by game design experts, epidemiologists, and software developers.