Dan Yamin

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.

Epidemiological and Viral Genomic Sequence Analysis of the 2014 Ebola Outbreak Reveals Clustered Transmission

Using Ebolavirus genomic and epidemiological data, we conducted the first joint analysis in which both data types were used to fit dynamic transmission models for an ongoing outbreak. Our results indicate that transmission is clustered, highlighting a potential bias in medical demand forecasts, and provide the first empirical estimate of underreporting.

Quantifying Poverty as a Driver of Ebola Transmission

Background Poverty has been implicated as a challenge in the control of the current Ebola outbreak in West Africa. Although disparities between affected countries have been appreciated, disparities within West African countries have not been investigated as drivers of Ebola transmission. To quantify the role that poverty plays in the transmission of Ebola, we analyzed heterogeneity of Ebola incidence and transmission factors among over 300 communities, categorized by socioeconomic status (SES), within Montserrado County, Liberia. Methodology/Principal Findings We evaluated 4,437 Ebola cases reported between February 28, 2014 and December 1, 2014 for Montserrado County to determine SES-stratified temporal trends and drivers of Ebola transmission. A dataset including dates of symptom onset, hospitalization, and death, and specified community of residence was used to stratify cases into high, middle and low SES. Additionally, information about 9,129 contacts was provided for a subset of 1,585 traced individuals. To evaluate transmission within and across socioeconomic subpopulations, as well as over the trajectory of the outbreak, we analyzed these data with a time-dependent stochastic model. Cases in the most impoverished communities reported three more contacts on average than cases in high SES communities (p<0.001). Our transmission model shows that infected individuals from middle and low SES communities were associated with 1.5 (95% CI: 1.4–1.6) and 3.5 (95% CI: 3.1–3.9) times as many secondary cases as those from high SES communities, respectively. Furthermore, most of the spread of Ebola across Montserrado County originated from areas of lower SES. Conclusions/Significance Individuals from areas of poverty were associated with high rates of transmission and spread of Ebola to other regions. Thus, Ebola could most effectively be prevented or contained if disease interventions were targeted to areas of extreme poverty and funding was dedicated to development projects that meet basic needs.

Incentives' Effect in Influenza Vaccination Policy

In the majority of developed countries, the level of influenza vaccination coverage in all age groups is suboptimal. Hence, the authorities offer different kinds of incentives for people to become vaccinated such as subsidizing immunization or placing immunization centers in malls to make the process more accessible. We built a theoretical epidemiological game model to find the optimal incentive for vaccination and the corresponding expected level of vaccination coverage. The model was supported by survey data from questionnaires about peoples perceptions about influenza and the vaccination against it. Results suggest that the optimal magnitude of the incentives should be greater when less contagious seasonal strains of influenza are involved and greater for the nonelderly population rather than the elderly, and should rise as high as

Harnessing Case Isolation and Ring Vaccination to Control Ebola

57 per vaccinated individual so that all children between the ages of six months and four years will be vaccinated. This paper was accepted by Yossi Aviv, operations management.

Vaccination strategies against respiratory syncytial virus

As a devastating Ebola outbreak in West Africa continues, non-pharmaceutical control measures including contact tracing, quarantine, and case isolation are being implemented. In addition, public health agencies are scaling up efforts to test and deploy candidate vaccines. Given the experimental nature and limited initial supplies of vaccines, a mass vaccination campaign might not be feasible. However, ring vaccination of likely case contacts could provide an effective alternative in distributing the vaccine. To evaluate ring vaccination as a strategy for eliminating Ebola, we developed a pair approximation model of Ebola transmission, parameterized by confirmed incidence data from June 2014 to January 2015 in Liberia and Sierra Leone. Our results suggest that if a combined intervention of case isolation and ring vaccination had been initiated in the early fall of 2014, up to an additional 126 cases in Liberia and 560 cases in Sierra Leone could have been averted beyond case isolation alone. The marginal benefit of ring vaccination is predicted to be greatest in settings where there are more contacts per individual, greater clustering among individuals, when contact tracing has low efficacy or vaccination confers post-exposure protection. In such settings, ring vaccination can avert up to an additional 8% of Ebola cases. Accordingly, ring vaccination is predicted to offer a moderately beneficial supplement to ongoing non-pharmaceutical Ebola control efforts.

Social contacts, vaccination decisions and influenza in Japan

Significance The WHO estimates that respiratory syncytial virus (RSV) vaccination will be available in the next 5–10 y. To evaluate the population effectiveness of an RSV vaccination program in the United States, we developed a transmission model that integrates data on daily infectious viral load and behavior changes while symptomatic. Our model simulations demonstrate that vaccinating children younger than 5 y of age will be the most efficient and effective way to prevent RSV infection in both children and older adults, a result that is robust across the US states considered. Accordingly, the population burden of RSV would be most effectively reduced if current vaccine candidates were to focus on children. Respiratory syncytial virus (RSV) is the most common cause of US infant hospitalization. Additionally, RSV is responsible for 10,000 deaths annually among the elderly across the United States, and accounts for nearly as many hospitalizations as influenza. Currently, several RSV vaccine candidates are under development to target different age groups. To evaluate the potential effectiveness of age-specific vaccination strategies in averting RSV incidence, we developed a transmission model that integrates data on daily infectious viral load and changes of behavior associated with RSV symptoms. Calibrating to RSV weekly incidence rates in Texas, California, Colorado, and Pennsylvania, we show that in all states considered, an infected child under 5 y of age is more than twice as likely as a person over 50 y of age to transmit the virus. Geographic variability in the effectiveness of a vaccination program across states arises from interplay between seasonality patterns, population demography, vaccination uptake, and vaccine mechanism of action. Regardless of these variabilities, our analysis showed that allocating vaccine to children under 5 y of age would be the most efficient strategy per dose to avert RSV in both children and adults. Furthermore, due to substantial indirect protection, the targeting of children is even predicted to reduce RSV in the elderly more than directly vaccinating the elderly themselves. Our results can help inform ongoing clinical trials and future recommendations on RSV vaccination.

Interrupting Ebola Transmission in Liberia Through Community-Based Initiatives

Background Contact patterns and vaccination decisions are fundamental to transmission dynamics of infectious diseases. We report on age-specific contact patterns in Japan and their effect on influenza vaccination behaviour. Methods Japanese adults (N=3146) were surveyed in Spring 2011 to assess the number of their social contacts within a 24 h period, defined as face-to-face conversations within 2 m, and gain insight into their influenza-related behaviour. We analysed the duration and location of contacts according to age. Additionally, we analysed the probability of vaccination and influenza infection in relation to the number of contacts controlling for individuals characteristics. Results The mean and median reported numbers of daily contacts were 15.3 and 12.0, respectively. School-aged children and young adults reported the greatest number of daily contacts, and individuals had the most contacts with those in the same age group. The age-specific contact patterns were different between men and women, and differed between weekdays and weekends. Children had fewer contacts between the same age groups during weekends than during weekdays, due to reduced contacts at school. The probability of vaccination increased with the number of contacts, controlling for age and household size. Influenza infection among unvaccinated individuals was higher than for those vaccinated, and increased with the number of contacts. Conclusions Contact patterns in Japan are age and gender specific. These contact patterns, as well as their interplay with vaccination decisions and infection risks, can help inform the parameterisation of mathematical models of disease transmission and the design of public health policies, to control disease transmission.

Retrospective Analysis of the 2014–2015 Ebola Epidemic in Liberia

On 6 March 2014, Ebola virus disease spread from Guinea to Liberia, sparking an unprecedented outbreak. At the peak of the epidemic in western Africa, Liberia was the most affected country (1). Despite its extraordinary resource constraintsper capita gross domestic product is much lower than that of Guinea or Sierra Leone (2)Liberias steep epidemic trajectory was reversed several weeks before that of those countries. This article details the community-based initiative (CBI) that was instrumental to the shift in transmission dynamics. In the design of public health strategies, organizational and cultural sensitivity, as well as an awareness of infrastructure constraints, are fundamental to promoting adherence to policy recommendations (3, 4). Inadequate consideration of these factors hindered the initial top-down Ebola response in western Africa. Slum and ethnic settlements tend to have cultures characterized by rituals of prevailing tribal groups and a strong sense of connectedness among persons who have lived together for decades. Externally led interventions, such as quarantine and body collection, that did not engage regarded community leaders led to distrust for and underuse of these interventions. In addition, the infrastructural constraints of these impoverished communities, including the lack of running water and overcrowding, made such recommendations as hand washing and isolation of the sick inapplicable (Table). Table. Community Reaction to Misalignment Between Cultural Practice and Public Health Policies In August 2014, unmitigated transmission in West Point, Monrovias largest slum, was recognized as a potentially insurmountable threat to disease containment. Here, we focus on the outbreak in West Point as a case study that can inform the future control of Ebola in the worlds most challenging settings. A Case Study: West Point The first suspected case in West Point was reported to the National Ebola Incident Management System on 6 August 2014. The slum was particularly vulnerable to intense transmission given the cramped conditions of more than 80000 persons living in less than a half square kilometer without municipal water or a sewage system and only 1 physician for the entire community (5). Poverty compounded the distrust of external authorities, including skepticism about whether the Ebola outbreak was real (6). Initially, no Ebola treatment unit facilities were available in West Point to isolate infected patients. A holding center was opened for interim isolation. When it began to receive patients from outside of West Point, unrest erupted over concern that disease was being imported into the community. On 18 August, the center was ransacked and contaminated materials were looted. To prevent the spread of Ebola, the government quarantined the entire slum on 20 August using police and military forces, leading to clashes with the community and the death of a boy shot in his legs. Members of the Ebola Incident Management System with ties to the local community recognized that a less-invasive approach would be needed to achieve acceptance of the interventions. Although West Point residents typically resist government policies, trust for community leaders is unwavering. Harnessing the cooperation of local leaders to build trust between the community and public health authorities was paramount to the successful control of Ebola. On 17 September, a district-wide program was piloted to enhance awareness of and participation in response efforts, with an external team of public health advisors providing guidance (Figure). Coordinators from the Ministry of Health identified districts with active Ebola transmission to engage with the CBI. Community, tribal, and religious leaders, as well as other stakeholders, were invited to an open meeting where they were encouraged to express their thoughts about the Ebola response and propose ways to facilitate public health efforts. The community then organized a team to comprehensively map the area to assess human resource requirements. Figure. Components of the CBI. CBI = community-based initiative. The community leaders who attended the initial meeting recruited community members for a 1-day training session on active surveillance. Each CBI-employed community member was assigned approximately 25 households for daily surveillance. At the training session, county-level CBI coordinators reviewed data collection forms with community members. Supervisors received and were trained to use a mobile telephone preloaded with a user-friendly application for submitting data in real time to inform rapid-response action by case investigation, contact tracing, burial, and ambulance teams. Trained community members collected forms each day that reported on the sick, dead, visitors, and other factors that influenced Ebola transmission in their communities. A hierarchical reporting and coordinating structure was executed, with the community members submitting these forms to their immediate supervisors, who sent aggregate data to the district-level supervisors. The United Nations Development Programme funded CBI training and employed community members and coordinators. Altogether, 6500 persons were employed and equipped for 6 months at a cost of approximately

Cost-effectiveness of influenza vaccination in prior pneumonia patients in Israel.

65000 (U.S. dollars). Within 24 hours of launching the CBI in West Point, 42 persons with Ebola-like symptoms were identified and transported to Ebola treatment units. Furthermore, the CBI uncovered 34 deaths from suspected Ebola and several secret burials that had not been reported as a result of mistrust of authorities or concern about stigma. The CBI team and local leaders developed a procedure to deliver food and offer social support to make household-based quarantine of contacts feasible. Ultimately, the door-to-door assessments in West Point were accomplished by 152 active case finders, 15 psychosocial support workers, 8 supervisors, and 2 district leaders. After the success in West Point, the Liberian Ministry of Health commissioned a scale-up of the CBI to Ebola hotspots throughout Montserrado County. By 21 September, the CBI was deployed in 6 districts. The implementation of these initiatives substantially improved contact-tracing cooperation and adherence to case isolation. For cases in the districts where the CBI was being implemented, the average number of contacts reported increased from 7.6 to 9.9 and mean time from symptom onset to isolation decreased from 6.5 to 4.7 days. This decrease in duration until isolation is crucial to reduce transmission, because viral load and thus infectiousness of patients with Ebola increase substantially over the course of infection (7). Latest Outbreak In July 2015, a new outbreak emerged in Margibi County, Liberia, where a teenage boy with Ebola was misdiagnosed with malaria. Contact-tracing efforts and the CBI were deployed in parallel to follow known contacts and conduct community-driven surveillance, respectively. A CBI team of 75 community members visited 397 households in the vicinity, identifying 126 contacts who were followed for 21 days. This community mobilization curtailed transmission before any tertiary cases emerged. The success of this effort starkly contrasts with the spiraling epidemic observed a year before, fueled by a similar number of secondary cases before the CBI was initiated. Conclusion By engaging and empowering local communities, the CBI was instrumental to cooperation with contact tracing and accelerating case isolation. This strategy is both feasible and effective in the resource-constrained settings of many western African countries. Leaders of the Liberian CBI are currently advising the Sierra Leone Ministry of Health on the implementation of community-driven efforts to control its outbreak that has yet to be extinguished. More broadly, the momentum of community involvement spurred by the Ebola response provides an opportunity for sustained improvement in the public health infrastructure in Liberia and other western African countries.