Publications by authors named "Jose Lourenço"

54 Publications

Sixteen novel lineages of SARS-CoV-2 in South Africa.

Nat Med 2021 Feb 2. Epub 2021 Feb 2.

KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.

The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90). Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref. ), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref. ), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020 (ref. ).
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http://dx.doi.org/10.1038/s41591-021-01255-3DOI Listing
February 2021

Potential impact of individual exposure histories to endemic human coronaviruses on age-dependent severity of COVID-19.

BMC Med 2021 01 12;19(1):19. Epub 2021 Jan 12.

Department of Zoology, University of Oxford, Oxford, UK.

Background: Cross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission.

Methods: We use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection.

Results: We hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model.

Conclusions: This study provides a "proof of possibility" for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.
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http://dx.doi.org/10.1186/s12916-020-01887-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801230PMC
January 2021

Asynchronicity of endemic and emerging mosquito-borne disease outbreaks in the Dominican Republic.

Nat Commun 2021 01 8;12(1):151. Epub 2021 Jan 8.

Instituto de Medicina Tropical & Salud Global, Universidad Iberoamericana, Santo Domingo, Dominican Republic.

Mosquito-borne viruses threaten the Caribbean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.
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http://dx.doi.org/10.1038/s41467-020-20391-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794562PMC
January 2021

The global impact of the COVID-19 pandemic on the prevention, diagnosis and treatment of hepatitis B virus (HBV) infection.

BMJ Glob Health 2021 01;6(1)

Department of Zoology, University of Oxford, Oxford, UK

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a myriad of interventions with the urgent aim of reducing the public health impact of this virus. However, a wealth of evidence both from high-income and low-income countries is accruing on the broader consequences of such interventions on economic and public health inequalities, as well as on pre-existing programmes targeting endemic pathogens. We provide an overview of the impact of the ongoing COVID-19 pandemic on hepatitis B virus (HBV) programmes globally, focusing on the possible consequences for prevention, diagnosis and treatment. Ongoing disruptions to infrastructure, supply chains, services and interventions for HBV are likely to contribute disproportionately to the short-term incidence of chronic hepatitis B, providing a long-term source of onward transmission to future generations that threatens progress towards the 2030 elimination goals.
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http://dx.doi.org/10.1136/bmjgh-2020-004275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786543PMC
January 2021

Estimating the false-negative test probability of SARS-CoV-2 by RT-PCR.

Euro Surveill 2020 12;25(50)

Department of Zoology, University of Oxford, Oxford, United Kingdom.

BackgroundReverse-transcription PCR (RT-PCR) assays are used to test for infection with the SARS-CoV-2 virus. RT-PCR tests are highly specific and the probability of false positives is low, but false negatives are possible depending on swab type and time since symptom onset.AimTo determine how the probability of obtaining a false-negative test in infected patients is affected by time since symptom onset and swab type.MethodsWe used generalised additive mixed models to analyse publicly available data from patients who received multiple RT-PCR tests and were identified as SARS-CoV-2 positive at least once.ResultsThe probability of a positive test decreased with time since symptom onset, with oropharyngeal (OP) samples less likely to yield a positive result than nasopharyngeal (NP) samples. The probability of incorrectly identifying an uninfected individual due to a false-negative test was considerably reduced if negative tests were repeated 24 hours later. For a small false-positive test probability (<0.5%), the true number of infected individuals was larger than the number of positive tests. For a higher false-positive test probability, the true number of infected individuals was smaller than the number of positive tests.ConclusionNP samples are more sensitive than OP samples. The later an infected individual is tested after symptom onset, the less likely they are to test positive. This has implications for identifying infected patients, contact tracing and discharging convalescing patients who are potentially still infectious.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.50.2000568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812420PMC
December 2020

Characterising West Nile virus epidemiology in Israel using a transmission suitability index.

Euro Surveill 2020 11;25(46)

Porter School of the Environment and Earth Sciences, Tel Aviv University, Tel Aviv, Israel.

BackgroundClimate is a major factor in the epidemiology of West Nile virus (WNV), a pathogen increasingly pervasive worldwide. Cases increased during 2018 in Israel, the United States and Europe.AimWe set to retrospectively understand the spatial and temporal determinants of WNV transmission in Israel, as a case study for the possible effects of climate on virus spread.MethodsWe employed a suitability index to WNV, parameterising it with prior knowledge pertaining to a bird reservoir and species, using local time series of temperature and humidity as inputs. The predicted suitability index was compared with confirmed WNV cases in Israel (2016-2018).ResultsThe suitability index was highly associated with WNV cases in Israel, with correlation coefficients of 0.91 (p value = 4 × 10- 5), 0.68 (p = 0.016) and 0.9 (p = 2 × 10- 4) in 2016, 2017 and 2018, respectively. The fluctuations in the number of WNV cases between the years were explained by higher area under the index curve. A new WNV seasonal mode was identified in the south-east of Israel, along the Great Rift Valley, characterised by two yearly peaks (spring and autumn), distinct from the already known single summer peak in the rest of Israel.ConclusionsBy producing a detailed geotemporal estimate of transmission potential and its determinants in Israel, our study promotes a better understanding of WNV epidemiology and has the potential to inform future public health responses. The proposed approach further provides opportunities for retrospective and prospective mechanistic modelling of WNV epidemiology and its associated climatic drivers.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.46.1900629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678037PMC
November 2020

Early transmission of SARS-CoV-2 in South Africa: An epidemiological and phylogenetic report.

Int J Infect Dis 2021 Feb 12;103:234-241. Epub 2020 Nov 12.

KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Centre for Aids Programme of Research in South Africa (CAPRISA), Durban, South Africa; Department of Global Health, University of Washington, Seattle, Washington, USA. Electronic address:

Objectives: The Network for Genomic Surveillance in South Africa (NGS-SA) was formed to investigate the introduction and understand the early transmission dynamics of the SARS-CoV-2 epidemic in South-Africa.

Design: This paper presents the first results from this group, which is a molecular epidemiological study of the first 21 SARS-CoV-2 whole genomes sampled in the first port of entry - KwaZulu-Natal (KZN) - during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), it aimed to shed light on the patterns of infections in South Africa.

Results: Two of the largest provinces - Gauteng and KZN - had a slow growth rate for the number of detected cases, while the epidemic spread faster in the Western Cape and Eastern Cape. The estimates of transmission potential suggested a decrease towards R = 1 since the first cases and deaths, but a subsequent estimated R average of 1.39 between 6-18 May 2020. It was also demonstrated that early transmission in KZN was associated with multiple international introductions and dominated by lineages B1 and B. Evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic was also provided.

Conclusion: The COVID-19 pandemic in South Africa was very heterogeneous in its spatial dimension, with many distinct introductions of SARS-CoV2 in KZN and evidence of nosocomial transmission, which inflated early mortality in KZN. The epidemic at the local level was still developing and NGS-SA aimed to clarify the dynamics in South Africa and devise the most effective measures as the outbreak evolved.
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http://dx.doi.org/10.1016/j.ijid.2020.11.128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658561PMC
February 2021

Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020.

Euro Surveill 2020 10;25(42)

Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.42.2000685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651873PMC
October 2020

The ongoing COVID-19 epidemic in Minas Gerais, Brazil: insights from epidemiological data and SARS-CoV-2 whole genome sequencing.

Emerg Microbes Infect 2020 Dec;9(1):1824-1834

Laboratório Central de Saúde Pública, Fundação Ezequiel Dias, Belo Horizonte, Brazil.

The recent emergence of a coronavirus (SARS-CoV-2), first identified in the Chinese city of Wuhan in December 2019, has had major public health and economic consequences. Although 61,888 confirmed cases were reported in Brazil by 28 April 2020, little is known about the SARS-CoV-2 epidemic in this country. To better understand the recent epidemic in the second most populous state in southeast Brazil - Minas Gerais (MG) - we sequenced 40 complete SARS-CoV-2 genomes from MG cases and examined epidemiological data from three Brazilian states. Both the genome analyses and the geographical distribution of reported cases indicate for multiple independent introductions into MG. Epidemiological estimates of the reproductive number (R) using different data sources and theoretical assumptions suggest the potential for sustained virus transmission despite a reduction in R from the first reported case to the end of April 2020. The estimated date of SARS-CoV-2 introduction into Brazil was consistent with epidemiological data from the first case of a returned traveller from Lombardy, Italy. These findings highlight the nature of the COVID-19 epidemic in MG and reinforce the need for real-time and continued genomic surveillance strategies to better understand and prepare for the epidemic spread of emerging viral pathogens..
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http://dx.doi.org/10.1080/22221751.2020.1803146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473129PMC
December 2020

Early transmission of SARS-CoV-2 in South Africa: An epidemiological and phylogenetic report.

medRxiv 2020 May 30. Epub 2020 May 30.

KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Background: The emergence of a novel coronavirus, SARS-CoV-2, in December 2019, progressed to become a world pandemic in a few months and reached South Africa at the beginning of March. To investigate introduction and understand the early transmission dynamics of the virus, we formed the South African Network for Genomics Surveillance of COVID (SANGS_COVID), a network of ten government and university laboratories. Here, we present the first results of this effort, which is a molecular epidemiological study of the first twenty-one SARS-CoV-2 whole genomes sampled in the first port of entry, KwaZulu-Natal (KZN), during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), we aim to shed light on the patterns of infections that define the epidemic in South Africa.

Methods: R was calculated using positive cases and deaths from reports provided by the four major provinces. Molecular epidemiology investigation involved sequencing viral genomes from patients in KZN using ARCTIC protocols and assembling whole genomes using meticulous alignment methods. Phylogenetic analysis was performed using maximum likelihood (ML) and Bayesian trees, lineage classification and molecular clock calculations.

Findings: The epidemic in South Africa has been very heterogeneous. Two of the largest provinces, Gauteng, home of the two large metropolis Johannesburg and Pretoria, and KwaZulu-Natal, home of the third largest city in the country Durban, had a slow growth rate on the number of detected cases. Whereas, Western Cape, home of Cape Town, and the Eastern Cape provinces the epidemic is spreading fast. Our estimates of transmission potential for South Africa suggest a decreasing transmission potential towards R=1 since the first cases and deaths have been reported. However, between 06 May and 18 May 2020, we estimate that R was on average 1.39 (1.04 - 2.15, 95% CI). We also demonstrate that early transmission in KZN, and most probably in all main regions of SA, was associated with multiple international introductions and dominated by lineages B1 and B. The study also provides evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic, which inflated early mortality in KZN.

Interpretation: This first report of SANGS_COVID consortium focuses on understanding the epidemic heterogeneity and introduction of SARS-CoV-2 strains in the first month of the epidemic in South Africa. The early introduction of SARS-CoV-2 in KZN included caused a localized outbreak in a hospital, provides potential explanations for the initially high death rates in the province. The current high rate of transmission of COVID-19 in the Western Cape and Eastern Cape highlights the crucial need to strength local genomic surveillance in South Africa.
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http://dx.doi.org/10.1101/2020.05.29.20116376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273273PMC
May 2020

MVSE: An R-package that estimates a climate-driven mosquito-borne viral suitability index.

Methods Ecol Evol 2019 Aug 19;10(8):1357-1370. Epub 2019 Jun 19.

Department of Zoology University of Oxford Oxford UK.

Viruses, such as dengue, Zika, yellow fever and chikungunya, depend on mosquitoes for transmission. Their epidemics typically present periodic patterns, linked to the underlying mosquito population dynamics, which are known to be driven by natural climate fluctuations. Understanding how climate dictates the timing and potential of viral transmission is essential for preparedness of public health systems and design of control strategies. While various alternative approaches have been proposed to estimate local transmission potential of such viruses, few open-source, ready to use and freely available software tools exist.We developed the osquito-borne iral uitability stimator (MVSE) software package for the R programming environment. MVSE estimates the index P, a novel suitability index based on a climate-driven mathematical expression for the basic reproductive number of mosquito-borne viruses. By accounting for local humidity and temperature, as well as viral, vector and human priors, the index P can be estimated for specific host and viral species in different regions of the globe.We describe the background theory, empirical support and biological interpretation of the index P. Using real-world examples spanning multiple epidemiological contexts, we further demonstrate MVSE's basic functionality, research and educational potentials.
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http://dx.doi.org/10.1111/2041-210X.13205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202302PMC
August 2019

High residual carriage of vaccine-serotype Streptococcus pneumoniae after introduction of pneumococcal conjugate vaccine in Malawi.

Nat Commun 2020 05 6;11(1):2222. Epub 2020 May 6.

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi's 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3-5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6-8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with high-income settings, there is high residual VT carriage 3.6-7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.
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http://dx.doi.org/10.1038/s41467-020-15786-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203201PMC
May 2020

Hepatitis B virus seroepidemiology data for Africa: Modelling intervention strategies based on a systematic review and meta-analysis.

PLoS Med 2020 04 21;17(4):e1003068. Epub 2020 Apr 21.

Nuffield Department of Medicine, University of Oxford, Medawar Building for Pathogen Research, Oxford, United Kingdom.

Background: International Sustainable Development Goals (SDGs) for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In African populations, infant immunisation has been fundamental to reducing incident infections in children, but overall population prevalence of chronic hepatitis B (CHB) infection remains high. In high-prevalence populations, adult catch-up vaccination has sometimes been deployed, but an alternative Test and Treat (T&T) approach could be used as an intervention to interrupt transmission. Universal T&T has not been previously evaluated as a population intervention for HBV infection, despite high-profile data supporting its success with human immunodeficiency virus (HIV).

Methods And Findings: We set out to investigate the relationship between prevalence of HBV infection and exposure in Africa, undertaking a systematic literature review in November 2019. We identified published seroepidemiology data representing the period 1995-2019 from PubMed and Web of Science, including studies of adults that reported prevalence of both hepatitis B surface antigen (HBsAg; prevalence of HBV infection) and antibody to hepatitis B core antigen (anti-HBc; prevalence of HBV exposure). We identified 96 studies representing 39 African countries, with a median cohort size of 370 participants and a median participant age of 34 years. Using weighted linear regression analysis, we found a strong relationship between the prevalence of infection (HBsAg) and exposure (anti-HBc) (R2 = 0.45, p < 0.001). Region-specific differences were present, with estimated CHB prevalence in Northern Africa typically 30% to 40% lower (p = 0.007) than in Southern Africa for statistically similar exposure rates, demonstrating the need for intervention strategies to be tailored to individual settings. We applied a previously published mathematical model to investigate the effect of interventions in a high-prevalence setting. The most marked and sustained impact was projected with a T&T strategy, with a predicted reduction of 33% prevalence by 20 years (95% CI 30%-37%) and 62% at 50 years (95% CI 57%-68%), followed by routine neonatal vaccination and prevention of mother to child transmission (PMTCT; at 100% coverage). In contrast, the impact of catch-up vaccination in adults had a negligible and transient effect on population prevalence. The study is constrained by gaps in the published data, such that we could not model the impact of antiviral therapy based on stratification by specific clinical criteria and our model framework does not include explicit age-specific or risk-group assumptions regarding force of transmission.

Conclusions: The unique data set collected in this study highlights how regional epidemiology data for HBV can provide insights into patterns of transmission, and it provides an evidence base for future quantitative research into the most effective local interventions. In combination with robust neonatal immunisation programmes, ongoing PMTCT efforts, and the vaccination of high-risk groups, diagnosing and treating HBV infection is likely to be of most impact in driving advances towards elimination targets at a population level.
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http://dx.doi.org/10.1371/journal.pmed.1003068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173646PMC
April 2020

Genomic and Epidemiological Surveillance of Zika Virus in the Amazon Region.

Cell Rep 2020 02;30(7):2275-2283.e7

Laboratório de Flavivírus, Instituto Oswaldo Cruz Fiocruz, Rio de Janeiro, Brazil; Laboratório de Genética Celular e Molecular, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Zika virus (ZIKV) has caused an explosive epidemic linked to severe clinical outcomes in the Americas. As of June 2018, 4,929 ZIKV suspected infections and 46 congenital syndrome cases had been reported in Manaus, Amazonas, Brazil. Although Manaus is a key demographic hub in the Amazon region, little is known about the ZIKV epidemic there, in terms of both transmission and viral genetic diversity. Using portable virus genome sequencing, we generated 59 ZIKV genomes in Manaus. Phylogenetic analyses indicated multiple introductions of ZIKV from northeastern Brazil to Manaus. Spatial genomic analysis of virus movement among six areas in Manaus suggested that populous northern neighborhoods acted as sources of virus transmission to other neighborhoods. Our study revealed how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil.
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http://dx.doi.org/10.1016/j.celrep.2020.01.085DOI Listing
February 2020

Hospital discharges in urban sanitation systems: Long-term monitoring of wastewater resistome and microbiota in relationship to their eco-exposome.

Water Res X 2020 May 4;7:100045. Epub 2020 Feb 4.

University Limoges, INSERM, CHU Limoges, RESINFIT, U1092, F-87000, Limoges, France.

Wastewaters (WW) are important sources for the dissemination of antimicrobial resistance (AMR) into the environment. Hospital WW (HWW) contain higher loads of micro-pollutants and AMR markers than urban WW (UWW). Little is known about the long-term dynamics of H and U WW and the impact of their joined treatment on the general burden of AMR. Here, we characterized the resistome, microbiota and eco-exposome signature of 126 H and U WW samples treated separately for three years, and then mixed, over one year. Multi-variate analysis and machine learning revealed a robust signature for each WW with no significant variation over time before mixing, and once mixed, both WW closely resembled Urban signatures. We demonstrated a significant impact of pharmaceuticals and surfactants on the resistome and microbiota of H and U WW. Our results present considerable targets for AMR related risk assessment of WW.
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http://dx.doi.org/10.1016/j.wroa.2020.100045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013138PMC
May 2020

Return of the founder Chikungunya virus to its place of introduction into Brazil is revealed by genomic characterization of exanthematic disease cases.

Emerg Microbes Infect 2020 27;9(1):53-57. Epub 2019 Dec 27.

Coordenação Geral de Vigilância de Arboviroses (CGARB).

Between June 2017 and August 2018, several municipalities located in Bahia state (Brazil) reported a large increase in the number of patients presenting with febrile illness similar to that of arboviral infections. Using a combination of portable whole genome sequencing, molecular clock and epidemiological analyses, we revealed the return of the CHIKV-ECSA genotype into Bahia. Our results show local persistence of lineages in some municipalities and the re-introduction of new epidemiological strains from different Brazilian regions, highlighting a complex dynamic of transmission between epidemic seasons and sampled locations. Estimated climate-driven transmission potential of CHIKV remained at similar levels throughout the years, such that large reductions in the total number of confirmed cases suggests a slow, but gradual accumulation of herd-immunity over the 4 years of the epidemic in Bahia after its introduction in 2014. Bahia remains a reservoir of the genetic diversity of CHIKV in the Americas, and genomic surveillance strategies are essential to assist in monitoring and understanding arboviral transmission and persistence both locally and over large distances.
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http://dx.doi.org/10.1080/22221751.2019.1701954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968431PMC
March 2020

Distinct rates and patterns of spread of the major HIV-1 subtypes in Central and East Africa.

PLoS Pathog 2019 12 6;15(12):e1007976. Epub 2019 Dec 6.

KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, Belgium.

Since the ignition of the HIV-1 group M pandemic in the beginning of the 20th century, group M lineages have spread heterogeneously throughout the world. Subtype C spread rapidly through sub-Saharan Africa and is currently the dominant HIV lineage worldwide. Yet the epidemiological and evolutionary circumstances that contributed to its epidemiological expansion remain poorly understood. Here, we analyse 346 novel pol sequences from the DRC to compare the evolutionary dynamics of the main HIV-1 lineages, subtypes A1, C and D. Our results place the origins of subtype C in the 1950s in Mbuji-Mayi, the mining city of southern DRC, while subtypes A1 and D emerged in the capital city of Kinshasa, and subtypes H and J in the less accessible port city of Matadi. Following a 15-year period of local transmission in southern DRC, we find that subtype C spread at least three-fold faster than other subtypes circulating in Central and East Africa. In conclusion, our results shed light on the origins of HIV-1 main lineages and suggest that socio-historical rather than evolutionary factors may have determined the epidemiological fate of subtype C in sub-Saharan Africa.
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http://dx.doi.org/10.1371/journal.ppat.1007976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897401PMC
December 2019

Measuring Mosquito-borne Viral Suitability in Myanmar and Implications for Local Zika Virus Transmission.

PLoS Curr 2018 Sep 28;10. Epub 2018 Sep 28.

Department of Zoology, University of Oxford, Oxford, UK.

Introduction: In South East Asia, mosquito-borne viruses (MBVs) have long been a cause of high disease burden and significant economic costs. While in some SEA countries the epidemiology of MBVs is spatio-temporally well characterised and understood, in others such as Myanmar our understanding is largely incomplete.

Materials And Methods: Here, we use a simple mathematical approach to estimate a climate-driven suitability index aiming to better characterise the intrinsic, spatio-temporal potential of MBVs in Myanmar.

Results: Results show that the timing and amplitude of the natural oscillations of our suitability index are highly informative for the temporal patterns of DENV case counts at the country level, and a mosquito-abundance measure at a city level. When projected at fine spatial scales, the suitability index suggests that the time period of highest MBV transmission potential is between June and October independently of geographical location. Higher potential is nonetheless found along the middle axis of the country and in particular in the southern corridor of international borders with Thailand.

Discussion: This research complements and expands our current understanding of MBV transmission potential in Myanmar, by identifying key spatial heterogeneities and temporal windows of importance for surveillance and control. We discuss our findings in the context of Zika virus given its recent worldwide emergence, public health impact, and current lack of information on its epidemiology and transmission potential in Myanmar. The proposed suitability index here demonstrated is applicable to other regions of the world for which surveillance data is missing, either due to lack of resources or absence of an MBV of interest.
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http://dx.doi.org/10.1371/currents.outbreaks.7a6c64436a3085ebba37e5329ba169e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472868PMC
September 2018

Effect of dietary supplementation of palm kernel cake on ovarian and hepatic function in buffalo (Bubalus bubalis).

Anim Reprod Sci 2019 May 14;204:76-85. Epub 2019 Mar 14.

São Paulo State University (UNESP), School of Agrarian and Veterinary Sciences, Department of Preventive Veterinary Medicine and Animal Reproduction, Campus Jaboticabal, São Paulo, Brazil; São Paulo State University (UNESP), School of Veterinary Medicine, Laboratory of Reproductive Physiology, Campus Araçatuba, São Paulo, Brazil.

To determine the optimal inclusion amount of palm kernel cake (PKC) in a buffalo diet, in the present study there was evaluation of the ovarian activity, metabolism and hepatic function of females that were treated to synchronize the time of ovulation. Twenty-four estrous-cyclic and non-lactating Murrah buffalo with a mean age of 5.7 years were supplemented with 0%, 0.25%, 0.5% and 1% of their body weight (BW) with PKC. Animals were subjected to the Ovsynch protocol (beginning of protocol = D0). The ovaries were examined and the blood was collected on D10 (follicular phase) and D17 (luteal phase). Follicular and luteal development and serum progesterone concentrations were not affected by diet (P > 0.05). Serum concentrations of cholesterol were greater in animals supplemented with PKC in amounts at 0.5% of BW or less with PKC, regardless of the phase of the estrous cycles when evaluations occurred (P < 0.05). Concentrations of HDL-cholesterol were similar (P > 0.05) during the follicular and luteal phases. Triglyceride concentrations increased linearly (P = 0.03) as percentage of PKC inclusion diets increased during the follicular phase, but were similar in the luteal phase (60.0 mg/dL; P = 0.51). Amount of PKC supplementation did not affect the concentrations of alanine aminotransferase, but there was a greater amount of aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) during both phases of the estrous cycle (P < 0.05). Animals supplemented at 1.0% of BW with PKC had greater AST and GGT concentrations than what is recommended for buffalo. The results of the present study indicate PKC supplementation of buffalo diets does not affect the development of the ovarian follicle and corpus luteum nor the peripheral concentration of progesterone, even though there are greater serum concentrations of total cholesterol and triglycerides. Because the amount of PKC supplementation in the present study does not result in hepatic dysfunction when fed at the 0.5% of BW amount, it is suggested that this agro-industrial byproduct of high nutritional value may be a new alternative for dietary supplementation of grazing buffalo.
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http://dx.doi.org/10.1016/j.anireprosci.2019.03.007DOI Listing
May 2019

The effect of ventricular volume increase in the amplitude of intracranial pressure.

Comput Methods Biomech Biomed Engin 2019 Jul 1;22(9):889-900. Epub 2019 Apr 1.

d Center for Computational and Stochastic Mathematics - CEMAT, Department of Mathematics, Instituto Superior Técnico , University of Lisbon , Lisboa , Portugal.

We study the impact of vascular pulse in the cerebrospinal fluid (CSF) pressure measured on the lateral cerebral ventricles, as well as its sensitivity with respect to ventricular volume change. Recent studies have addressed the importance of the compliance capacity in the brain and its relation to arterial pulse abortion in communicating hydrocephalus. Nevertheless, this mechanism is not fully understood. We propose a fluid-structure interaction (FSI) model on a 3 D idealized geometry based on realistic physiological and morphological parameters. The computational model describes the pulsatile deformation of the third ventricle due to arterial pulse and the resulting CSF dynamics inside brain pathways. The results show that when the volume of lateral ventricles increases up to 3.5 times, the amplitudes of both average and maximum pressure values, computed on the lateral ventricles surface, substantially decrease. This indicates that the lateral ventricles expansion leads to a dumping effect on the pressure exerted on the walls of the ventricles. These results strengthen the possibility that communicant hydrocephalus may, in fact, be a natural response to reduce abnormal high intracranial pressure (ICP) amplitude. This conclusion is in accordance with recent hypotheses suggesting that communicant hydrocephalus is related to a disequilibrium in brain compliance capacity.
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http://dx.doi.org/10.1080/10255842.2019.1587413DOI Listing
July 2019

Identifying genes associated with invasive disease in S. pneumoniae by applying a machine learning approach to whole genome sequence typing data.

Sci Rep 2019 03 11;9(1):4049. Epub 2019 Mar 11.

University of Oxford, Department of Zoology, Oxford, UK.

Streptococcus pneumoniae, a normal commensal of the upper respiratory tract, is a major public health concern, responsible for substantial global morbidity and mortality due to pneumonia, meningitis and sepsis. Why some pneumococci invade the bloodstream or CSF (so-called invasive pneumococcal disease; IPD) is uncertain. In this study we identify genes associated with IPD. We transform whole genome sequence (WGS) data into a sequence typing scheme, while avoiding the caveat of using an arbitrary genome as a reference by substituting it with a constructed pangenome. We then employ a random forest machine-learning algorithm on the transformed data, and find 43 genes consistently associated with IPD across three geographically distinct WGS data sets of pneumococcal carriage isolates. Of the genes we identified as associated with IPD, we find 23 genes previously shown to be directly relevant to IPD, as well as 18 uncharacterized genes. We suggest that these uncharacterized genes identified by us are also likely to be relevant for IPD.
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http://dx.doi.org/10.1038/s41598-019-40346-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411942PMC
March 2019

Genomic, epidemiological and digital surveillance of Chikungunya virus in the Brazilian Amazon.

PLoS Negl Trop Dis 2019 03 7;13(3):e0007065. Epub 2019 Mar 7.

Department of Zoology, University of Oxford, South Parks Road, Oxford, United Kingdom.

Background: Since its first detection in the Caribbean in late 2013, chikungunya virus (CHIKV) has affected 51 countries in the Americas. The CHIKV epidemic in the Americas was caused by the CHIKV-Asian genotype. In August 2014, local transmission of the CHIKV-Asian genotype was detected in the Brazilian Amazon region. However, a distinct lineage, the CHIKV-East-Central-South-America (ECSA)-genotype, was detected nearly simultaneously in Feira de Santana, Bahia state, northeast Brazil. The genomic diversity and the dynamics of CHIKV in the Brazilian Amazon region remains poorly understood despite its importance to better understand the epidemiological spread and public health impact of CHIKV in the country.

Methodology/principal Findings: We report a large CHIKV outbreak (5,928 notified cases between August 2014 and August 2018) in Boa vista municipality, capital city of Roraima's state, located in the Brazilian Amazon region. We generated 20 novel CHIKV-ECSA genomes from the Brazilian Amazon region using MinION portable genome sequencing. Phylogenetic analyses revealed that despite an early introduction of the Asian genotype in 2015 in Roraima, the large CHIKV outbreak in 2017 in Boa Vista was caused by an ECSA-lineage most likely introduced from northeastern Brazil. Epidemiological analyses suggest a basic reproductive number of R0 of 1.66, which translates in an estimated 39 (95% CI: 36 to 45) % of Roraima's population infected with CHIKV-ECSA. Finally, we find a strong association between Google search activity and the local laboratory-confirmed CHIKV cases in Roraima.

Conclusions/significance: This study highlights the potential of combining traditional surveillance with portable genome sequencing technologies and digital epidemiology to inform public health surveillance in the Amazon region. Our data reveal a large CHIKV-ECSA outbreak in Boa Vista, limited potential for future CHIKV outbreaks, and indicate a replacement of the Asian genotype by the ECSA genotype in the Amazon region.
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http://dx.doi.org/10.1371/journal.pntd.0007065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424459PMC
March 2019

HBV vaccination and PMTCT as elimination tools in the presence of HIV: insights from a clinical cohort and dynamic model.

BMC Med 2019 02 21;17(1):43. Epub 2019 Feb 21.

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.

Background: Sustainable Development Goals set a challenge for the elimination of hepatitis B virus (HBV) infection as a public health concern by the year 2030. Deployment of a robust prophylactic vaccine and enhanced interventions for prevention of mother to child transmission (PMTCT) are cornerstones of elimination strategy. However, in light of the estimated global burden of 290 million cases, enhanced efforts are required to underpin optimisation of public health strategy. Robust analysis of population epidemiology is particularly crucial for populations in Africa made vulnerable by HIV co-infection, poverty, stigma and poor access to prevention, diagnosis and treatment.

Methods: We here set out to evaluate the current and future role of HBV vaccination and PMTCT as tools for elimination. We first investigated the current impact of paediatric vaccination in a cohort of children with and without HIV infection in Kimberley, South Africa. Second, we used these data to inform a new parsimonious model to simulate the ongoing impact of preventive interventions. By applying these two approaches in parallel, we are able to determine both the current impact of interventions, and the future projected outcome of ongoing preventive strategies over time.

Results: Existing efforts have been successful in reducing paediatric prevalence of HBV infection in this setting to < 1%, demonstrating the success of the existing vaccine campaign. Our model predicts that, if consistently deployed, combination efforts of vaccination and PMTCT can significantly reduce population prevalence (HBsAg) by 2030, such that a major public health impact is possible even without achieving elimination. However, the prevalence of HBV e-antigen (HBeAg)-positive carriers will decline more slowly, representing a persistent population reservoir. We show that HIV co-infection significantly reduces titres of vaccine-mediated antibody, but has a relatively minor role in influencing the projected time to elimination. Our model can also be applied to other settings in order to predict impact and time to elimination based on specific interventions.

Conclusions: Through extensive deployment of preventive strategies for HBV, significant positive public health impact is possible, although time to HBV elimination as a public health concern is likely to be substantially longer than that proposed by current goals.
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http://dx.doi.org/10.1186/s12916-019-1269-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383254PMC
February 2019

Reverse immunodynamics: a new method for identifying targets of protective immunity.

Sci Rep 2019 02 15;9(1):2164. Epub 2019 Feb 15.

Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK.

Despite a dramatic increase in our ability to catalogue variation among pathogen genomes, we have made far fewer advances in using this information to identify targets of protective immunity. Epidemiological models predict that strong immune selection can cause antigenic variants to structure into genetically discordant sets of antigenic types (e.g. serotypes). A corollary of this theory is that targets of immunity may be identified by searching for non-overlapping associations of amino acids among co-circulating antigenic variants. We propose a novel population genetics methodology that combines such predictions with phylogenetic analyses to identify genetic loci (epitopes) under strong immune selection. We apply this concept to the AMA-1 protein of the malaria parasite Plasmodium falciparum and find evidence of epitopes among certain regions of low variability which could render them ideal vaccine candidates. The proposed method can be applied to a myriad of multi-strain pathogens for which vast amounts of genetic data has been collected in recent years.
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http://dx.doi.org/10.1038/s41598-018-37288-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377634PMC
February 2019

A naturally protective epitope of limited variability as an influenza vaccine target.

Nat Commun 2018 09 21;9(1):3859. Epub 2018 Sep 21.

Department of Zoology, University of Oxford, Oxford, OX1 3PS, UK.

Current antigenic targets for influenza vaccine development are either highly immunogenic epitopes of high variability or conserved epitopes of low immunogenicity. This requires continuous update of the variable epitopes in the vaccine formulation or boosting of immunity to invariant epitopes of low natural efficacy. Here we identify a highly immunogenic epitope of limited variability in the head domain of the H1 haemagglutinin protein. We show that a cohort of young children exhibit natural immunity to a set of historical influenza strains which they could not have previously encountered and that this is partially mediated through the epitope. Furthermore, vaccinating mice with these epitope conformations can induce immunity to human H1N1 influenza strains that have circulated since 1918. The identification of epitopes of limited variability offers a mechanism by which a universal influenza vaccine can be created; these vaccines would also have the potential to protect against newly emerging influenza strains.
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http://dx.doi.org/10.1038/s41467-018-06228-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155085PMC
September 2018

Epidemiology of the Zika Virus Outbreak in the Cabo Verde Islands, West Africa.

PLoS Curr 2018 Mar 15;10. Epub 2018 Mar 15.

Department of Zoology, University of Oxford, Oxford, United Kingdom.

Introduction: The Zika virus (ZIKV) outbreak in the island nation of Cabo Verde was of unprecedented magnitude in Africa and the first to be associated with microcephaly in the continent.

Methods: Using a simple mathematical framework we present a first epidemiological assessment of attack and observation rates from 7,580 ZIKV notified cases and 18 microcephaly reports between July 2015 and May 2016.

Results: In line with observations from the Americas and elsewhere, the single-wave Cabo Verdean ZIKV epidemic was characterized by a basic reproductive number of 1.85 (95% CI, 1.5 - 2.2), with overall the attack rate of 51.1% (range 42.1 - 61.1) and observation rate of 2.7% (range 2.29 - 3.33).

Conclusion: Current herd-immunity may not be sufficient to prevent future small-to-medium epidemics in Cabo Verde. Together with a small observation rate, these results highlight the need for rapid and integrated epidemiological, molecular and genomic surveillance to tackle forthcoming outbreaks of ZIKV and other arboviruses.
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http://dx.doi.org/10.1371/currents.outbreaks.19433b1e4d007451c691f138e1e67e8cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866102PMC
March 2018

Challenges in dengue research: A computational perspective.

Evol Appl 2018 04 5;11(4):516-533. Epub 2017 Nov 5.

Centre for Mathematics and the Environment University of Exeter Penryn UK.

The dengue virus is now the most widespread arbovirus affecting human populations, causing significant economic and social impact in South America and South-East Asia. Increasing urbanization and globalization, coupled with insufficient resources for control, misguided policies or lack of political will, and expansion of its mosquito vectors are some of the reasons why interventions have so far failed to curb this major public health problem. Computational approaches have elucidated on dengue's population dynamics with the aim to provide not only a better understanding of the evolution and epidemiology of the virus but also robust intervention strategies. It is clear, however, that these have been insufficient to address key aspects of dengue's biology, many of which will play a crucial role for the success of future control programmes, including vaccination. Within a multiscale perspective on this biological system, with the aim of linking evolutionary, ecological and epidemiological thinking, as well as to expand on classic modelling assumptions, we here propose, discuss and exemplify a few major computational avenues-real-time computational analysis of genetic data, phylodynamic modelling frameworks, within-host model frameworks and GPU-accelerated computing. We argue that these emerging approaches should offer valuable research opportunities over the coming years, as previously applied and demonstrated in the context of other pathogens.
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http://dx.doi.org/10.1111/eva.12554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891037PMC
April 2018

A multi-country study of dengue vaccination strategies with Dengvaxia and a future vaccine candidate in three dengue-endemic countries: Vietnam, Thailand, and Colombia.

Vaccine 2018 04 21;36(17):2346-2355. Epub 2018 Mar 21.

Department of Zoology, University of Oxford, Oxford, UK.

Background: The dengue vaccination era began when Dengvaxia (CYD-TDV) became available in 2016. In addition, several second-generation vaccine candidates are currently in phase 3 trials, suggesting that a broader availability of dengue vaccines may be possible in the near future. Advancing on the recent WHO-SAGE recommendations for the safe and effective use of CYD-TDV at the regional level on average, this study investigates the vaccination impacts and cost-effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a country-specific manner for three endemic countries: Vietnam, Thailand, and Colombia.

Methods: The vaccination impacts of CYD-TDV and NVC were derived by fitting the empirical seroprevalence rates of 9 year olds into an individual-based meta-population transmission model, previously used for the WHO-SAGE working group. The disability-adjusted life years were estimated by applying country-specific parametric values. The cost-effectiveness analyses of four intervention strategies in combination with routine and catch-up campaigns were compared for both vaccines to inform decision makers regarding the most suitable immunization program in each of the three countries.

Results And Conclusion: Both CYD-TDV and NVC could be cost-effective at the DALY threshold cost of $2000 depending upon vaccination costs. With CYD-TDV, targeting 9 year olds in routine vaccination programs and 10-29 year olds as a one-off catch-up campaign was the most cost-effective strategy in all three countries. With NVC, while the most cost-effective strategy was to vaccinate 9-29 and 9-18 year olds in Vietnam and Thailand respectively, vaccinating younger age cohorts between 1 and 5 years old in Colombia was more cost-effective than other strategies. Given that three countries will soon face decisions regarding whether and how to incorporate CYD-TDV or future dengue vaccines into their budget-constrained national immunization programs, the current study outcomes can be used to help decision makers understand the expected impacts and cost-effectiveness of such vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2018.03.002DOI Listing
April 2018

Vaccination can drive an increase in frequencies of antibiotic resistance among nonvaccine serotypes of .

Proc Natl Acad Sci U S A 2018 03 6;115(12):3102-3107. Epub 2018 Mar 6.

Department of Zoology, University of Oxford, Oxford OX2 6GG, United Kingdom.

The bacterial pathogen is a major public health concern, being responsible for more than 1.5 million deaths annually through pneumonia, meningitis, and septicemia. Available vaccines target only a subset of serotypes, so vaccination is often accompanied by a rise in the frequency of nonvaccine serotypes. Epidemiological studies suggest that such a change in serotype frequencies is often coupled with an increase of antibiotic resistance among nonvaccine serotypes. Building on previous multilocus models for bacterial pathogen population structure, we have developed a theoretical framework incorporating variation of serotype and antibiotic resistance to examine how their associations may be affected by vaccination. Using this framework, we find that vaccination can result in a rapid increase in the frequency of preexisting resistant variants of nonvaccine serotypes due to the removal of competition from vaccine serotypes.
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http://dx.doi.org/10.1073/pnas.1718712115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866575PMC
March 2018

Adjustable Strabismus Surgery under Topical Anesthesia: Alignment in Supine vs Seated Position.

Strabismus 2018 03 9;26(1):28-32. Epub 2018 Jan 9.

a Ocular Motility Section, Department of Ophthalmology , Hospital General Universitario Gregorio Marañón , Madrid , Spain.

Purpose: To compare ocular deviation in the operating room depending on whether the patient is in supine decubitus or seated after single-stage adjustable strabismus surgery under topical anesthesia.

Material And Method: We performed a prospective observational study of 30 patients with horizontal and/or vertical strabismus who underwent single stage adjustable strabismus surgery under topical anesthesia. Both distance and near deviation were evaluated before surgery, during surgery in both positions (seated and supine), and at 1 day, 1 month, and 3 months after surgery. A final horizontal deviation <10 pd and a vertical deviation <5 pd without diplopia was considered to be a good outcome (3 months after surgery).

Results: The mean age of the sample was 55 years and 76.7% were women. Most had esotropia (70%). The most frequently used surgical combination was the medial rectus and lateral rectus (36.7%). Surgical adjustment was necessary in 40% of cases. Mean preoperative deviation was 21.9 ± 12.63 pd (distance) and 20.66 ± 4.76 (near). Deviation with the patient supine was 8 ± 8.25 pd (distance) and 7.26 ± 5.81 (near). Deviation with the patient seated was 8.13 pd±8.38 (distance) and 8.5 ± 7.41 (near). There was no significant difference between the positions. Outcome was favorable in 70% of patients; this percentage increased to 83.33% at 1 day, 1 month, and 3 months after surgery.

Conclusions: No statistically significant differences were found between ocular deviations in the seated or supine position in the operating room. Outcome was favorable in most cases 3 months after surgery. Intraoperative ocular deviation was not a predictor of outcome.
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http://dx.doi.org/10.1080/09273972.2017.1423362DOI Listing
March 2018