• Unifying the epidemiological and evolutionary dynamics of pathogens.

    3 July 2018

    A key priority for infectious disease research is to clarify how pathogen genetic variation, modulated by host immunity, transmission bottlenecks, and epidemic dynamics, determines the wide variety of pathogen phylogenies observed at scales that range from individual host to population. We call the melding of immunodynamics, epidemiology, and evolutionary biology required to achieve this synthesis pathogen "phylodynamics." We introduce a phylodynamic framework for the dissection of dynamic forces that determine the diversity of epidemiological and phylogenetic patterns observed in RNA viruses of vertebrates. A central pillar of this model is the Evolutionary Infectivity Profile, which captures the relationship between immune selection and pathogen transmission.

  • Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean.

    3 July 2018

    Several human genetic disorders of hemoglobin have risen in frequency because of the protection they offer against death from malaria, sickle-cell anemia being a canonical example. Here we address the issue of why this highly protective mutant, present at high frequencies in subSaharan Africa, is uncommon in Mediterranean populations that instead harbor a diverse range of thalassemic hemoglobin disorders. We demonstrate that these contrasting profiles of malaria-protective alleles can arise and be stably maintained by two well-documented phenomena: an alleviation of the clinical severity of alpha- and beta-thalassemia in compound thalassemic genotypes and a cancellation of malaria protection when alpha-thalassemia and the sickle-cell trait are coinherited. The complex distribution of globin mutants across Africa and the Mediterranean can therefore be explained by their specific intracellular interactions.

  • Distinct Zika Virus Lineage in Salvador, Bahia, Brazil.

    3 July 2018

    Sequencing of isolates from patients in Bahia, Brazil, where most Zika virus cases in Brazil have been reported, resulted in 11 whole and partial Zika virus genomes. Phylogenetic analyses revealed a well-supported Bahia-specific Zika virus lineage, which indicates sustained Zika virus circulation in Salvador, Bahia's capital city, since mid-2014.

  • Increasing prevalence of HIV-1 subtype A in Greece: estimating epidemic history and origin.

    3 July 2018

    BACKGROUND: In North America and Europe, human immunodeficiency virus (HIV)-1 infection has typically been dominated by subtype B transmission. More recently, however, non-B subtypes have been increasingly reported in Europe. METHODS: We analyzed 1158 HIV-1-infected individuals in Greece by DNA sequencing and phylogenetic analyses of protease and partial reverse-transcriptase regions. RESULTS: We found that the prevalence of non-B subtypes has increased over time and that this significant trend can be mainly attributed to subtype A, which eventually surpassed subtype B in prevalence in 2004 (42% and 33%, respectively). Multivariate analysis revealed that the year of HIV diagnosis was independently associated with subtype A infection (odds ratio for being infected with subtype A for a 10-year increase in the time period of diagnosis, 2.09 [95% confidence interval, 1.36-3.24]; P<.001). Phylogenetic analysis revealed that the subtype A epidemic in Greece is the result of a single founder event. The date of the most recent common ancestor of the subtype A in Greece was estimated to be 1977.9 (95% highest posterior density interval, 1973.7-1981.9). CONCLUSIONS: Subtype A circulates among the long-term residents of Greece. This is in contrast to the situation in most European countries, in which infection with non-B genetic forms is associated either with being an immigrant or heterosexual or with intravenous drug use.

  • Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

    3 July 2018

    The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.

  • Viral gene sequences reveal the variable history of hepatitis C virus infection among countries.

    3 July 2018

    BACKGROUND: The analysis of molecular phylogenies estimated from the gene sequences of sampled viruses can provide important insights into epidemiological processes. METHODS: The demographic and migration histories of the prevalent hepatitis C virus (HCV) subtypes 1a and 1b were inferred from viral gene sequences sampled in 5 countries. Estimated viral phylogenies were analyzed by use of methods based on parsimony and coalescent theory. RESULTS: The parsimony migration analysis suggested that the global subtype 1a and 1b epidemics are geographically structured, with asymmetrical movement of HCV strains among the sampled countries. The coalescent analysis indicated that subtype 1a infections in the United States, Brazil, and Indonesia began to increase exponentially during the 1940s and 1950s, whereas in Vietnam the increase began after the 1970s. In contrast, subtype 1b infections in these 4 countries and in Japan began to increase exponentially between 1880 and 1920, with a possible recent decrease in infection rates in Indonesia and Japan. In the United States, Brazil, and Vietnam, the epidemic growth rates for subtype 1a strains were higher than those for subtype 1b strains, whereas the growth rates were similar in Indonesia. CONCLUSIONS: The estimated histories of migration and population growth indicated that patterns of HCV transmission differ among countries and viral subtypes.

  • Phylodynamic analysis of the dissemination of HIV-1 CRF01_AE in Vietnam.

    3 July 2018

    To estimate the epidemic history of HIV-1 CRF01_AE in Vietnam and adjacent Guangxi, China, we determined near full-length nucleotide sequences of CRF01_AE from a total of 33 specimens collected in 1997-1998 from different geographic regions and risk populations in Vietnam. Phylogenetic and Bayesian molecular clock analyses were performed to estimate the date of origin of CRF01_AE lineages. Our study reconstructs the timescale of CRF01_AE expansion in Vietnam and neighboring regions and suggests that the series of CRF01_AE epidemics in Vietnam arose by the sequential introduction of founder strains into new locations and risk groups. CRF01_AE appears to have been present among heterosexuals in South-Vietnam for more than a decade prior to its epidemic spread in the early 1990s. In the late 1980s, the virus spread to IDUs in Southern Vietnam and subsequently in the mid-1990s to IDUs further north. Our results indicate the northward dissemination of CRF01_AE during this time.

  • Molecular epidemiology: HIV-1 and HCV sequences from Libyan outbreak.

    3 July 2018

    In 1998, outbreaks of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection were reported in children attending Al-Fateh Hospital in Benghazi, Libya. Here we use molecular phylogenetic techniques to analyse new virus sequences from these outbreaks. We find that the HIV-1 and HCV strains were already circulating and prevalent in this hospital and its environs before the arrival in March 1998 of the foreign medical staff (five Bulgarian nurses and a Palestinian doctor) who stand accused of transmitting the HIV strain to the children.

  • A reversal of fortunes: climate change 'winners' and 'losers' in Antarctic Peninsula penguins.

    3 July 2018

    Climate change is a major threat to global biodiversity. Antarctic ecosystems are no exception. Investigating past species responses to climatic events can distinguish natural from anthropogenic impacts. Climate change produces 'winners', species that benefit from these events and 'losers', species that decline or become extinct. Using molecular techniques, we assess the demographic history and population structure of Pygoscelis penguins in the Scotia Arc related to climate warming after the Last Glacial Maximum (LGM). All three pygoscelid penguins responded positively to post-LGM warming by expanding from glacial refugia, with those breeding at higher latitudes expanding most. Northern (Pygoscelis papua papua) and Southern (Pygoscelis papua ellsworthii) gentoo sub-species likely diverged during the LGM. Comparing historical responses with the literature on current trends, we see Southern gentoo penguins are responding to current warming as they did during post-LGM warming, expanding their range southwards. Conversely, Adélie and chinstrap penguins are experiencing a 'reversal of fortunes' as they are now declining in the Antarctic Peninsula, the opposite of their response to post-LGM warming. This suggests current climate warming has decoupled historic population responses in the Antarctic Peninsula, favoring generalist gentoo penguins as climate change 'winners', while Adélie and chinstrap penguins have become climate change 'losers'.