Genomic epidemiology reveals multiple introductions of Zika virus into the United States.

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.

Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis.

BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. METHODS: In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. FINDINGS: We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. INTERPRETATION: Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. FUNDING: Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development.

International travel between global urban centres vulnerable to yellow fever transmission.

OBJECTIVE: To examine the potential for international travel to spread yellow fever virus to cities around the world. METHODS: We obtained data on the international flight itineraries of travellers who departed yellow fever-endemic areas of the world in 2016 for cities either where yellow fever was endemic or which were suitable for viral transmission. Using a global ecological model of dengue virus transmission, we predicted the suitability of cities in non-endemic areas for yellow fever transmission. We obtained information on national entry requirements for yellow fever vaccination at travellers' destination cities. FINDINGS: In 2016, 45.2 million international air travellers departed from yellow fever-endemic areas of the world. Of 11.7 million travellers with destinations in 472 cities where yellow fever was not endemic but which were suitable for virus transmission, 7.7 million (65.7%) were not required to provide proof of vaccination upon arrival. Brazil, China, India, Mexico, Peru and the United States of America had the highest volumes of travellers arriving from yellow fever-endemic areas and the largest populations living in cities suitable for yellow fever transmission. CONCLUSION: Each year millions of travellers depart from yellow fever-endemic areas of the world for cities in non-endemic areas that appear suitable for viral transmission without having to provide proof of vaccination. Rapid global changes in human mobility and urbanization make it vital for countries to re-examine their vaccination policies and practices to prevent urban yellow fever epidemics.

Rates of genetic consultation in high-grade serous ovarian cancer patients in the era of PARP inhibitor therapy: A population-based study.

OBJECTIVE: The American Society of Clinical Oncology recommends all patients with high-grade serous ovarian carcinoma (HGSC) undergo germline genetic testing. Genetic consultation rates in Ontario, Canada, only reached 13.3% in 2011. In 2016, PARP inhibitor maintenance therapy became available in Ontario for BRCA-positive HGSC patients. Given expanding treatment options, we re-examined genetic consultation rates among HGSC patients. METHODS: This retrospective cohort study identified patients diagnosed with HGSC between 2012 and 2019 using population-based administrative data from Ontario. Genetics consultations were identified using Ontario Health Insurance Plan billing codes. Consultation rates over time were analyzed using Cochran-Armitage trend test and segmental regression analysis. Multivariable analysis identified factors associated with attending genetics consultation. RESULTS: This study included 4645 HGSC patients. The mean age was 64.2 years (±SD 12.3); 56.3% had stage 3-4 disease. Overall, approximately 35% attended genetics consultations. The genetic consultation rate per year increased significantly from 21.6% to 42.6% (P < 0.001). Shorter times between diagnosis and genetics consult were observed after PARP inhibitors became available (68.1 vs 34.1 weeks, P < 0.001). Patients treated at designated cancer centers (odds ratio [OR] 2.11, P < 0.001), diagnosed in later years (OR 1.33, P < 0.001), and from higher income groups (P < 0.05) were more likely to attend genetics consultation; older patients were less likely (OR 0.98, P < 0.001). After PARP inhibitors became available, consultation rates plateaued (P < 0.001). CONCLUSIONS: Between 2012 and 2019, genetic consultation rates improved significantly among HGSC patients; however, a large proportion of patients never attended consultation. Further exploration of barriers to care is warranted to improve consultation rates and ensure equitable access to care.

Effect of seasonal influenza vaccination on influenza symptom severity among children in Hutterite communities: Follow-up study of a randomized trial.

BACKGROUND: We investigated whether influenza vaccination reduces symptom severity among children who develop laboratory-confirmed influenza, and whether this association differed between influenza vaccine formulations. METHODS: We performed a retrospective cohort study using data from two blinded cluster randomized control trials of influenza vaccines in Hutterite colonies. In trial 1, children received trivalent inactivated influenza vaccine (TIV) or hepatitis A vaccine. In trial 2, children received trivalent live attenuated (TLAIV) or TIV. We assessed four outcomes (total number of symptoms, number of respiratory symptoms, number of systemic symptoms, and duration of symptoms) among children with PCR-confirmed influenza. We utilized two-sample t tests to quantify the relationship between vaccine group and outcome. We performed multivariable strain-specific analyses, controlling for age and season. RESULTS: TIV vs. Hep A vaccine: Among vaccinated children, 200 confirmed influenza infections were observed across 3014 person-seasons. Vaccine type (TIV vs. Hep A vaccine) did not significantly affect the number of respiratory or systemic symptoms, nor duration of symptoms (P > .05). TLAIV vs. TIV: Among 1186 children who received a study vaccine, 166 confirmed influenza infections were observed. TLAIV recipients experienced fewer total, respiratory, and systemic symptoms compared to TIV recipients (P < .05 for all). TLAIV-associated attenuation of symptom severity was observed in influenza B or A/H1N1 infections, but not H3. CONCLUSIONS: Seasonal influenza vaccine did not consistently attenuate symptom severity in the context of vaccine failure; however, TLAIV offered superior severity attenuation compared to TIV. Our results challenge the dictum that influenza vaccine reduces the severity of symptoms even when the vaccine fails to prevent influenza.

Association between air travel and importation of chikungunya into the USA.

Background: During infectious disease outbreaks with pandemic potential, the number of air passengers travelling from the outbreak source to international destinations has been used as a proxy for disease importation risk to new locations. However, evaluations of the validity of this approach are limited. We sought to quantify the association between international air travel and disease importation using the 2014-2016 chikungunya outbreak in the Americas as a case study.Methods: We used country-level chikungunya case data to define a time period of epidemic activity for each of the 45 countries and territories in the Americas reporting outbreaks between 2014 and 2016. For each country, we identified airports within or proximate to areas considered suitable for chikungunya transmission and summed the number of commercial air passengers departing from these airports during the epidemic period to each US state. We used negative binomial models to quantify the association between the number of incoming air passengers from countries experiencing chikungunya epidemics and the annual rate of chikungunya importation into the USA at the state level.Results: We found a statistically significant positive association between passenger flows via airline travel from countries experiencing chikungunya epidemics and the number of imported cases in the USA at the state level (P < 0.0001). Additionally, we found that as the number of arriving airline passengers increased by 10%, the estimated number of imported cases increased by 5.2% (95% CI: 3.0-7.6).Conclusion: This validation study demonstrated that air travel was strongly associated with observed importation of chikungunya cases in the USA and can be a useful proxy for identifying areas at increased risk for disease importation. This approach may be useful for understanding exportation risk of other arboviruses.

Genomic and epidemiological characterisation of a dengue virus outbreak among blood donors in Brazil.

Outbreaks caused by Dengue, Zika and Chikungunya viruses can spread rapidly in immunologically naïve populations. By analysing 92 newly generated viral genome sequences from blood donors and recipients, we assess the dynamics of dengue virus serotype 4 during the 2012 outbreak in Rio de Janeiro. Phylogenetic analysis indicates that the outbreak was caused by genotype II, although two isolates of genotype I were also detected for the first time in Rio de Janeiro. Evolutionary analysis and modelling estimates are congruent, indicating a reproduction number above 1 between January and June, and at least two thirds of infections being unnoticed. Modelling analysis suggests that viral transmission started in early January, which is consistent with multiple introductions, most likely from the northern states of Brazil, and with an increase in within-country air travel to Rio de Janeiro. The combination of genetic and epidemiological data from blood donor banks may be useful to anticipate epidemic spread of arboviruses.