Transmission dynamics of Ebola virus disease and intervention effectiveness in Sierra Leone

Li-Qun Fang, Yang Yang, Jia-Fu Jiang, Hong-Wu Yao, David Kargbo, Xin-Lou Li, Bao-Gui Jiang, Brima Kargbo, Yi-Gang Tong, Ya-Wei Wang, Kun Liu, Abdul Kamara, Foday Dafae, Alex Kanu, Rui-Ruo Jiang, Ye Sun, Ruo-Xi Sun, Wan-Jun Chen, Mai-Juan Ma, Natalie E. Dean, Harold Thomas, Ira M. Longini, Jr., M. Elizabeth Halloran, Wu-Chun Cao

Proceedings of the National Academy of Sciences

March 28, 2016

abstract

Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014−2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission.

Using age-stratified incidence data to examine the transmission consequences of pertussis vaccination

J.C. Blackwood, D.A.T. Cummings, S. Iamsirithaworn, P. Rohani

Epidemics

March 19, 2016

ABSTRACT

Pertussis is a highly infectious respiratory disease that has been on the rise in many countries worldwide over the past several years. The drivers of this increase in pertussis incidence remain hotly debated, with a central and long-standing hypothesis that questions the ability of vaccines to eliminate pertussis transmission rather than simply modulate the severity of disease. In this paper, we present age-structured case notification data from all provinces of Thailand between 1981 and 2014, a period during which vaccine uptake rose substantially, permitting an evaluation of the transmission impacts of vaccination. Our analyses demonstrate decreases in incidence across all ages with increased vaccine uptake – an observation that is at odds with pertussis case notification data in a number of other countries. To explore whether these observations are consistent with a rise in herd immunity and a reduction in bacterial transmission, we analyze an age-structured model that incorporates contrasting hypotheses concerning the immunological and transmission consequences of vaccines. Our results lead us to conclude that the most parsimonious explanation for the combined reduction in incidence and the shift to older age groups in the Thailand data is vaccine-induced herd immunity.

Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture

Katherine S Xue, Kathryn A Hooper, Anja R Ollodart, Adam S Dingens, Jesse D Bloom

eLIFE

March 15, 2016

ABSTRACT

RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.

Transmissibility and Pathogenicity of Ebola Virus: A Systematic Review and Meta-analysis of Household Secondary Attack Rate and Asymptomatic Infection

Natalie E. Dean, M. Elizabeth Halloran, Yang Yang, Ira M. Longini

Clinical Infectious Diseases

March 13, 2016

abstract

Factors affecting our ability to control an Ebola outbreak include transmissibility of the virus and the proportion of transmissions occurring asymptomatically. We performed a meta-analysis of Ebola household secondary attack rate (SAR), disaggregating by type of exposure (direct contact, no direct contact, nursing care, direct contact but no nursing care). The estimated overall household SAR is 12.5% (95% confidence interval [CI], 8.6%–16.3%). Transmission was driven by direct contact, with little transmission occurring in its absence (SAR, 0.8% [95% CI, 0%–2.3%]). The greatest risk factor was the provision of nursing care (SAR, 47.9% [95% CI, 23.3%–72.6%]). There was evidence of a decline in household SAR for direct contact between 1976 and 2014 (P = .018). We estimate that 27.1% (95% CI, 14.5%–39.6%) of Ebola infections are asymptomatic. Our findings suggest that surveillance and containment measures should be effective for controlling Ebola.

Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses

Richard A. Neher, Trevor Bedford, Rodney S. Daniels, Colin A. Russell, Boris I. Shraiman

Proceedings of the National Academy of Sciences

March 4, 2016

Abstract

Human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and re-infect previously infected individuals. Antigenic properties are largely determined by the surface glycoprotein hemagglutinin (HA) and amino acid substitutions at exposed epitope sites in HA mediate loss of recognition by antibodies. Here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruses in a phylogenetic tree. This mapping onto the tree allows prediction of antigenicity from HA sequence data alone. The mapping can further be used to make predictions about the makeup of the future seasonal influenza virus population, and we compare predictions between models with serological and sequence data. To make timely model output readily available, we developed a web browser based application that visualizes antigenic data on a continuously updated phylogeny.

Quantifying and mitigating the effect of preferential sampling on phylodynamic inference

Michael D. Karcher, Julia A. Palacios, Trevor Bedford, Marc A. Suchard, Vladimir N. Minin

PLOS Computational Biology

March 3, 2016

Abstract

Phylodynamics seeks to estimate effective population size fluctuations from molecular sequences of individuals sampled from a population of interest. One way to accomplish this task formulates an observed sequence data likelihood exploiting a coalescent model for the sampled individuals' genealogy and then integrating over all possible genealogies via Monte Carlo or, less efficiently, by conditioning on one genealogy estimated from the sequence data. However, when analyzing sequences sampled serially through time, current methods implicitly assume either that sampling times are fixed deterministically by the data collection protocol or that their distribution does not depend on the size of the population. Through simulation, we first show that, when sampling times do probabilistically depend on effective population size, estimation methods may be systematically biased. To correct for this deficiency, we propose a new model that explicitly accounts for preferential sampling by modeling the sampling times as an inhomogeneous Poisson process dependent on effective population size. We demonstrate that in the presence of preferential sampling our new model not only reduces bias, but also improves estimation precision. Finally, we compare the performance of the currently used phylodynamic methods with our proposed model through clinically-relevant, seasonal human influenza examples.

Hemagglutinin Gene Clade 3C.2a Influenza A(H3N2) Viruses, Alachua County, Florida, USA, 2014–15

John A. Lednicky, Nicole M. Iovine, Joe Brew, Julia C. Loeb, Jonathan D. Sugimoto, Kenneth H. Rand, J. Glenn Morris

Emerging Infectious Diseases

January 29, 2016

ABSTRACT

Influenza A(H3N2) strains isolated during 2014–15 in Alachua County, Florida, USA, belonged to hemagglutinin gene clade 3C.2a. High rates of influenza-like illness and confirmed influenza cases in children were associated with a decrease in estimated vaccine effectiveness. Illnesses were milder than in 2013–14; severe cases were concentrated in elderly patients with underlying diseases.

The pertussis enigma: reconciling epidemiology, immunology and evolution

Matthieu Domenech de Cellès, 
Felicia M. G. Magpantay, Aaron A. King, Pejman Rohani

Proceedings B
Royal Society Publishing

January 13, 2016

ABSTRACT

Pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. Still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. Resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. In this review, we first present 1980–2012 incidence data from 63 countries and show that pertussis resurgence is not universal. We further argue that the large geographical variation in trends probably precludes a simple explanation, such as the transition from whole-cell to acellular pertussis vaccines. Reviewing available evidence, we then propose that prevailing views on pertussis epidemiology are inconsistent with both historical and contemporary data. Indeed, we summarize epidemiological evidence showing that natural infection and vaccination both appear to provide long-term protection against transmission and disease, so that previously infected or vaccinated adults contribute little to overall transmission at a population level. Finally, we identify several promising avenues that may lead to a consistent explanation of global pertussis epidemiology and to more effective control strategies.