Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Brief statement of the problem: Although we made significant scientific advances in our understanding of the natural history and epidemiology of Ebola virus during the 2013-2016 Ebola virus disease (EVD) epidemic in West Africa, Ebola virus research has almost exclusively focused on moderate to severe disease rather than asymptomatic and milder infections. Conceptualizing and studying asymptomatically or symptomatically infected individuals as two different groups of unrecognized, Ebola virus-infected individuals has a great potential for paradigm shifts in public health, clinical care, and global policies. There has been a growing body of literature demonstrating a significant burden of pauci-/asymptomatic infection and unrecognized EVD, but the public health and clinical consequences have been unclear, potentially leading to unknown transmission and untreated clinical sequelae. This dissertation has the following objectives: 1) to assess exposure risk in a dose-dependent relationship with severity of illness, 2) examine whether clinical sequelae occur after mild EVD, and 3) identify inflammatory markers that may partially explain how survivors recover from clinical sequelae. Description of the methods and procedures used to gather data or study the problem: This dissertation leverages two cohorts of Ebola cases and contacts. In Chapter 1, from September 2016 to July 2017, we conducted a cross-sectional, community-based study of Ebola virus disease (EVD) cases and household contacts of several transmission chains in Kono District, Sierra Leone. We used epidemiological surveys and blood samples to define severity of illness as no infection, pauci-/asymptomatic infection, unrecognized EVD, reported EVD cases who survived, or reported EVD decedents. We determine seropositivity with the Filovirus Animal Non-Clinical Group (FANG) EBOV glycoprotein IgG antibody test. We defined levels of exposure risk from eight questions and considered contact with body fluid as maximum exposure risk. In Chapter 2, from June 2015 through June 2017, we studied a cohort of EVD survivors and their contacts in Liberia. Surveys, current symptoms and physical exam findings, and serology characterized disease status of reported EVD, unrecognized EVD, pauci-/asymptomatic EBOV infection, or no infection. We pre-specified findings known to be differentially prevalent among EVD survivors than contacts. We estimated the prevalence and incidence of selected clinical findings by disease status. In Chapter 3, we used baseline data from a longitudinal cohort of confirmed EVD survivors (seropositive) and their uninfected contacts (seronegative) in Liberia to generate a cytokine profile from stored plasma samples. These data included a sub-cohort of men assessed for Ebola viral shedding in semen. We investigated pre-specified clinical findings previously reported to be differentially prevalent among EVD survivors. Outcomes were self-reported symptoms, physical examination findings, and viral persistence in semen. Using generalized estimating equations, we compared inflammatory markers among survivors and contacts; statistically significant markers (p<0.01) were assessed for associations among survivors with and without sequelae. Summary of the findings: In Chapter 1, this community-based study of EVD cases and contacts provides epidemiological evidence of a dose-dependent relationship between exposure risk and severity of illness, which may partially explain why pauci-/asymptomatic EBOV infection, less severe disease, and unrecognized EVD occurs. In Chapter 2, the findings provide evidence of post-EVD clinical sequelae among contacts with unrecognized EVD but not pauci-/asymptomatic EBOV infection. In Chapter 3, we found evidence of persistent inflammation among survivors, which may be partially explained by ongoing viral shedding. Multiple clinical sequelae were less likely to be associated with two macrophage and pro-inflammatory markers, suggesting that a process of downregulation may be occurring as these survivors experienced clinical recovery.

Background: In many parts of Sub-Saharan Africa, adolescent sexual and reproductive health is often of low political priority and there are often restrictive laws and policies that are in contradiction with international agreements and commitments.

Objectives: The main objectives of this dissertation research were 1) to apply the Public Arenas Model to appraise the environments, definitions, competition dynamics, principles of selection, and current actors involved in problem-solving and prioritizing adolescent pregnancy as a policy issue; 2) to qualitatively explore the generation, process, constraints, dilemmas, and institutionalization of political priority for adolescent sexual and reproductive health in Kenya, and 3) to compare pregnancy incidence among women using depo medroxy progesterone acetate levonorgesteral implants and intra uterine copper devices within a multicenter, open-label, randomized clinical trial.

Methods: The research used mixed research methodology. For Aim 1, We applied the Public Arenas Model to critically appraise the environments, definitions, competition dynamics, principles of selection, and current actors involved in problem-solving and prioritizing adolescent pregnancy as a policy issue. To achieve Aim 2, a postmodern, interpretive focused ethnographic approach was used. This included a critical review of the empirical and theoretical literature, existing national documents, and participant interviews. We used the Shiffman and Smith policy framework consisting of four categories—actor power, ideas, political contexts, and issue characteristics—to analyze factors that have shaped political prioritization of adolescent sexual and reproductive health. We undertook semi-structured interviews with members of adolescent sexual and reproductive health networks at the national level and conducted thematic analysis of the interviews. For Aim 3, we analyzed data from the ECHO Trial, which assessed HIV incidence among 7829 women from 12 sites in Eswatini, Kenya, South Africa, and Zambia who were seeking effective contraception and consented to be randomized to DMPA-IM, a copper IUD, or an LNG implant. Cox proportional hazards regression adjusted for condom use was used to compare pregnancy incidence during both perfect use (defined as from initiation of method until first discontinuation for any reason). Additional analyses explored more typical use (i.e., until decline or change to a different contraceptive method).

Summary of Findings:

In Aim 1, we found existing definitions center around adolescent pregnancy as a “disease” that needs prevention and treatment, socially deviant behavior that requires individual agency, and a national social concern that drains public resources and therefore needs to be regulated. These conflicting definitions contributed to the rarity of the topic achieving traction within the political agenda and may result in conflicting solutions, such as lowering the legal age of consenting to sex, while limiting access to contraceptive information and services to minors.

In Aim 2, we found that the adolescent sexual and reproductive health community was diverse and united in adoption of international norms and policies, but lacked policy champions to provide strong leadership, and policy windows were often missed. Community members lacked consensus on a cohesive public positioning of the problem. Moreover, the perception of adolescents as lacking political power made politicians reluctant to act on the existing data on the severity of adolescent SRH. There was also a lack of consensus on the nature of interventions to be implemented. The sectorial funding by donors and government treasury brought about tension within the different government ministries resulting in siloed approaches, lack of coordination, and overall inefficiency.

In Aim 3, 7710 women contributed to this analysis. Seventy pregnancies occurred during perfect use and 85 during more typical use. Perfect use pregnancy incidence rates were 0.61 per 100 woman-years for DMPA-IM (95% CI 0.36-0.96), 1.06 for copper IUD (95% CI 0.72-1.50), and 0.63 for LNG implants (95% CI 0.39-0.96); differences between methods were not statistically significant (p>0.05). Typical use incidence rates were generally similar, although slightly higher for copper IUD (1.11 per 100 woman-years, 95% CI 0.77-1.54).