OBJECTIVES:To describe, at patient-level detail, the determining events and factors involved in the development of a countryʼs HIV-1 epidemic.
DESIGN:Clinical information for all recorded Greenlandic ...HIV-1 patients was analysed and correlated with both novel and previously analysed pol sequences, representing more than half of the entire Greenlandic HIV-1 epidemic. Archival blood samples were sequenced to link early infection chain descriptions to the subsequent epidemic.
METHODS:In-depth phylogenetic analyses were used in synergy with clinical information to assess number of introductions of HIV-1 into Greenland, the source of geographic origin, time of epidemic introduction and its epidemiological characteristics such as initial transmission chain, geographic dispersal within Greenland, method of infection, cluster size, sociological and behavioural factors.
RESULTS:Despite its small population size and isolated geographic location, data support at least 25 introductions of HIV-1 into Greenland. Only a single of these led to an epidemic. This introduction occurred between 1985 and 1986, and the epidemic cluster is still active. Facilitating factors for the emergence and spread of the epidemic cluster include a rapid transition from MSM to heterosexual spread, high prevalence of other sexually transmitted diseases, rapid dispersal to larger cities and early emergence in a distinct subpopulation with high-risk behaviour including disregard for condomizing.
CONCLUSIONS:The synergistic use of disparate data categories yields such unique detail, that the Greenland epidemic now serves as a model example for the epidemic emergence of HIV-1 in a society. This renders it suitable for testing of present and future sequence-based epidemiological methodologies.
Highlights • Changes in healthcare delivery can bias vaccine impact estimates based on hospitalization data. • Improvements in primary care that reduce hospitalizations often coincide with vaccine ...introduction. • Vaccine benefits may be underestimated if hospitals are operating at full capacity. • Commonly used adjustments are not always sufficient to control for bias and confounding. • We suggest ways to strengthen vaccine impact assessments based on hospitalization data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure that the vaccine is effective and to quantify its impact. However, estimates from observational studies ...can be confounded by unrelated changes in healthcare utilization, changes in the underlying health of the population, or changes in reporting. Other diseases are often used to detect and adjust for these changes, but choosing an appropriate control disease a priori is a major challenge. The “synthetic controls” (causal impact) method, which was originally developed for website analytics and social sciences, provides an appealing solution. With this approach, potential comparison time series are combined into a composite and are used to generate a counterfactual estimate, which can be compared with the time series of interest after the intervention. We sought to estimate changes in hospitalizations for all-cause pneumonia associated with the introduction of pneumococcal conjugate vaccines (PCVs) in five countries in the Americas. Using synthetic controls, we found a substantial decline in hospitalizations for all-cause pneumonia in infants in all five countries (average of 20%), whereas estimates for young and middle-aged adults varied by country and were potentially influenced by the 2009 influenza pandemic. In contrast to previous reports, we did not detect a decline in all-cause pneumonia in older adults in any country. Synthetic controls promise to increase the accuracy of studies of vaccine impact and to increase comparability of results between populations compared with alternative approaches.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune ...selection in infants as longitudinal studies of infants are limited. Here, 1,210
and 1,264
sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in
evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.IMPORTANCEDespite increased coverage in antiretroviral therapy for the prevention of perinatal transmission, paediatric HIV-1 infection remains a significant public health concern, especially in areas of high HIV-1 prevalence. Understanding HIV-1 transmission and the subsequent virus adaptation from the mother to the infant's host environment, as well as the viral factors that affect disease outcome, is important for the development of early immune-directed interventions for infants. This study advances our understanding of vertical HIV-1 transmission, and how infant immune selection pressure is shaping the intra-host evolutionary dynamics of HIV-1.
Swine vesicular disease virus (SVDV) is an enterovirus that is both genetically and antigenically closely related to human coxsackievirus B5 within the Picornaviridae family. SVDV is the causative ...agent of a highly contagious (though rarely fatal) vesicular disease in pigs. We report a rapid method that is suitable for sequencing the complete protein-encoding sequences of SVDV isolates in which the RNA is relatively intact. The approach couples a single PCR amplification reaction, using only a single PCR primer set to amplify the near-complete SVDV genome, with deep-sequencing using a small fraction of the capacity of a Roche GS FLX sequencing platform. Sequences were initially verified through one of two criteria; either a match between a de novo assembly and a reference mapping, or a match between all of five different reference mappings performed against a fixed set of starting reference genomes with significant genetic distances within the same species of viruses. All reference mappings used an iterative method to avoid bias. Further verification was achieved through phylogenetic analysis against published SVDV genomes and additional Enterovirus B sequences. This approach allows high confidence in the obtained consensus sequences, as well as provides sufficiently high and evenly dispersed sequence coverage to allow future studies of intra-host variation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Pneumococcal conjugate vaccines (PCVs) prevent invasive pneumococcal disease and pneumonia. However, some low- and middle-income countries have yet to introduce PCV into their immunization ...programs due, in part, to lack of certainty about the potential impact. Assessing PCV benefits is challenging because specific data on pneumococcal disease is often lacking, and it can be difficult to separate the effects of factors other than the vaccine that could also affect pneumococcal disease rates.
METHODS:We assess PCV impact by combining Bayesian model averaging with change point models to estimate the timing and magnitude of vaccine-associated changes, while controlling for seasonality and other covariates. We applied our approach to monthly time series of age-stratified hospitalizations related to pneumococcal infection in children under 5 years of age in the United States, Brazil, and Chile.
RESULTS:Our method accurately detected changes in data in which we knew true and noteworthy changes occurred, i.e. in simulated data and for invasive pneumococcal disease. Moreover, 24 months after the vaccine introduction, we detected reductions of 14%, 9%, and 9% in the U.S., Brazil, and Chile, respectively, in all-cause pneumonia (ACP) hospitalizations for age group 0 to <1 years of age.
CONCLUSIONS:Our approach provides a flexible and sensitive method to detect changes in disease incidence that occur after the introduction of a vaccine or other intervention, while avoiding biases that exist in current approaches to time trend analyses.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Vaccine against Pneumococcal Pneumonia in Adults Weinberger, Daniel M; Bruhn, Christian A W; Shapiro, Eugene D
The New England journal of medicine,
07/2015, Volume:
373, Issue:
1
Journal Article
Molecular detection of viruses has been aided by high-throughput sequencing, permitting the genomic characterization of emerging strains. In this study, we comprehensively screened 500 respiratory ...secretions from children with upper and/or lower respiratory tract infections for viral pathogens. The viruses detected are described, including a divergent human parainfluenza virus type 4 from GS FLX pyrosequencing of 92 specimens. Complete full-genome characterization of the virus followed, using Single Molecule, Real-Time (SMRT) sequencing. Subsequent "primer walking" combined with Sanger sequencing validated the RS platform's utility in viral sequencing from complex clinical samples. Comparative genomics reveals the divergent strain clusters with the only completely sequenced HPIV4a subtype. However, it also exhibits various structural features present in one of the HPIV4b reference strains, opening questions regarding their lifecycle and evolutionary relationships among these viruses. Clinical data from patients infected with the strain, as well as viral prevalence estimates using real-time PCR, is also described.
Swine vesicular disease virus (SVDV) is a close relative of the human Enterovirus B serotype, coxsackievirus B5. As the etiological agent of a significant emergent veterinary disease, several studies ...have attempted to explain its origin. However, several key questions remain, including the full biological ancestry of the virus, and its geographical and temporal origin.
We sequenced near-complete genomes of 27 SVDV and 13 coxsackievirus B5 samples, all originally isolated between 1966 and 2006, and analysed these in conjunction with existing sequences and historical information.
While analyses incorporating 24 additional near-complete SVDV genomic sequences indicate clear signs of within-SVDV recombination, all 51 SVDV isolates remain monophyletic. This supports a hypothesis of a single anthroponotic transfer origin. Analysis of individual coding and non-coding regions supports that SVDV has a recombinant origin between coxsackievirus B5 and another Enterovirus B serotype, most likely coxsackievirus A9. Extensive Bayesian sequence-based analysis of the time of the most recent common ancestor of all analysed sequences places this within a few years around 1961. Epidemiological evidence points to China as an origin, but there are no available samples to test this conclusively.
Historical investigation and the clinical aspects of the involved Enterovirus B serotypes, makes the current results consistent with a hypothesis stating that SVDV originated through co-infection, recombination, and a single anthroponotic event, during large viral meningitis epidemics around 1960/1961 involving the ancestral serotypes. The exact geographical origin of SVDV may remain untestable due to historical aspects.
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