Biology subjects

Lourenco, J.

Publications and source records attributed to Lourenco, J..

12 recordsLinked to original sources

bioRxiv2018

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

BackgroundViruses 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.\n\nResultsWe developed the Mosquito-borne Viral Suitability Estimator (MVSE) software package for the R programming environment. The package estimates a suitability index based on a climate-driven mathematical expression for the basic reproductive number (R0) of a well established mathematical model for the transmission dynamics of mosquito-borne viruses. By accounting for local humidity and temperature, as well as viral, vector and human priors, suitability can be estimated for specific host and viral species, as well as different regions of the globe.\n\nConclusionsHere, we describe the background theory and biological interpretation of the new suitability index, as well as the implementation, basic functionality, research and educational potentials of the MVSE R-package. The package is freely available under the GPL 3.0 license.

epidemiology↗

bioRxiv2018

Identifying Streptococcus pneumoniae genes associated with invasive disease using pangenome-based whole genome sequence typing

Streptococcus pneumoniae is a normal commensal of the upper respiratory tract but can also invade the bloodstream or CSF (cerebrospinal fluid), causing invasive pneumococcal disease (IPD). In this study, we attempt to identify genes associated with IPD by applying a random forest machine-learning algorithm to whole genome sequence (WGS) data. We find 43 genes consistently associated with IPD across three geographically distinct WGS data sets of pneumococcal carriage isolates. Of these genes, 23 genes have previously shown to be directly relevant to IPD, while the other 18 are uncharacterized.

bioinformatics↗

bioRxiv2018

Genomic and epidemiological monitoring of yellow fever virus transmission potential

The yellow fever virus (YFV) epidemic that began in Dec 2016 in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes sp. vectors highlights the urgent need to monitor the risk of re-establishment of domestic YFV transmission in the Americas. We use a suite of epidemiological, spatial and genomic approaches to characterize YFV transmission. We show that the age- and sex-distribution of human cases in Brazil is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally using a new protocol reveals an early phase of sylvatic YFV transmission restricted to Minas Gerais, followed in late 2016 by a rise in viral spillover to humans, and the southwards spatial expansion of the epidemic towards previously YFV-free areas. Our results establish a framework for monitoring YFV transmission in real-time, contributing to the global strategy of eliminating future yellow fever epidemics.

epidemiology↗

bioRxiv2017

Measuring mosquito-borne viral suitability and its implications for Zika virus transmission in Myanmar

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.

epidemiology↗

bioRxiv2017

Identification of an epitope of limited variability under strong immune selection in the haemagglutinin head domain of H1N1 influenza

Antigenic targets of influenza vaccination are currently seen to be polarised between (i) highly immunogenic (and protective) epitopes of high variability, and (ii) conserved epitopes of low immunogenicity. This requires vaccines directed against the variable sites to be continuously updated, with the only other alternative being seen as the artificial boosting of immunity to invariant epitopes of low natural efficacy. However, theoretical models suggest that the antigenic evolution of influenza is best explained by postulating the existence of highly immunogenic epitopes of limited variability. Here we report the identification of such an epitope of limited variability in the head domain of the H1 haemagglutinin protein. We show that the epitope mediates immunity to historical influenza strains not previously seen by a cohort of young children. Furthermore, vaccinating mice with these epitope conformations can induce immunity to all the 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.

epidemiology↗

bioRxiv2017

Zika virus outbreak in Cabo Verde Islands, West Africa: early epidemiological findings

IntroductionThe 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.\n\nMethodsUsing 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.\n\nResultsIn 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).\n\nConclusionCurrent 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.

epidemiology↗

bioRxiv2017

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

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. We propose a novel methodology that combines predictions from epidemiological models with phylogenetic and structural analyses to identify such targets. Epidemiological models predict that strong immune selection can cause antigenic variants to exist in non-overlapping combinations. A corollary of this theory is that targets of immunity may be identified by searching for non-overlapping associations among antigenic variants. We applied this concept to the AMA-1 protein of the malaria parasite Plasmodium falciparum and found strong signatures of immune selection among certain regions of low variability which could render them ideal vaccine candidates.

epidemiology↗

bioRxiv2017

Utilising a Cohort Study of Hepatitis B Virus (HBV) Vaccine-Mediated Immunity in South African Children to Model Infection Dynamics: Can We Meet Global Targets for Elimination by 2030?

BackgroundSustainable 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.\n\nMethodsWe 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 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.\n\nResultsExisting 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 time to elimination based on specific interventions.\n\nConclusionsThrough 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.

microbiology↗

bioRxiv2017

Vaccination Can Drive An Increase In Frequencies Of Antibiotic Resistance Among Non-Vaccine Serotypes Of Streptococcus pneumoniae

The bacterial pathogen Streptococcus pneumoniae is a major public health concern, being responsible for more than 1.5 million deaths annually through pneumonia, meningitis and septicemia. In spite of vaccination efforts, pneumococcal carriage and disease remain high, since available vaccines target only a subset of serotypes and vaccination is often accompanied by a rise in non-vaccine serotypes. Epidemiological studies suggest that such a change in serotype frequencies is often coupled with an increase of antibiotic resistance among non-vaccine serotypes. Building on previous multi-locus models for bacterial pathogen population structure, we have developed a theoretical framework incorporating variation in serotype and antibiotic resistance to examine how their associations may be affected by vaccination. Using this framework, we find that vaccination can result in rapid increase in frequency of pre-existing resistant variants of non-vaccine serotypes due to the removal of competition from vaccine serotypes.

epidemiology↗

bioRxiv2017

Emergence and persistence of the Chikungunya virus East-Central-South-African genotype in Northeast Brazil

We investigate an outbreak of exanthematous illness in Maceio, Alagoas, using molecular surveillance. Of 273 samples, 76% tested RT-qPCR positive for Chikungunya virus. Phylogenetic analysis reveals that the outbreak was caused by the East-Central-South-African genotype, and that this lineage has likely persisted since mid-2014 in Northeast Brazil.\n\nArticle summary lineTransmission of the Chikungunya virus East-Central-South-African genotype has been ongoing in the Northeast region of Brazil since mid-2014.

epidemiology↗

bioRxiv2017

Epidemiological and ecological determinants of Zika virus transmission in an urban setting.

Zika has emerged as a global public health concern. Although its rapid geographic expansion can be attributed to the success of its Aedes mosquito vectors, local epidemiological drivers are still poorly understood. The city of Feira de Santana played a pivotal role in the early phases of the Chikungunya and Zika epidemics in Brazil. Here, using a climate-driven transmission model, we show that low Zika observation rates and a high vectorial capacity in this region were responsible for a high attack rate during the 2015 outbreak and the subsequent decline in cases in 2016, when the epidemic was peaking in the rest of the country. Our projections indicate that the balance between the loss of herd-immunity and the frequency of viral re-importation will dictate the transmission potential of Zika in this region in the near future. Sporadic outbreaks are expected but unlikely to be detected under current surveillance systems.

epidemiology↗

bioRxiv2016

Signatures of non-neutral processes within the population structure of Streptococcus pneumoniae

Populations of Streptococcus pneumoniae (SP) are typically structured into groups of closely related organisms or lineages, but it is not clear whether they are maintained by selection or neutral processes. Here, we attempt to address this question by applying a machine learning technique to SP whole genomes. Our results indicate that lineages evolved through immune selection on the groEL chaperone protein. The groEL protein is part of the groESL operon and enables a large range of proteins to fold correctly within the physical environment of the nasopharynx, thereby explaining why lineage structure is so stable within SP despite high levels of genetic transfer. SP is also antigenically diverse, exhibiting a variety of distinct capsular serotypes. Associations exist between lineage and capsular serotype but these can be easily perturbed, such as by vaccination. Overall, our analyses indicate that the evolution of SP can be conceptualized as the rearrangement of modular functional units occurring on several different timescales under different pressures: some patterns have locked in early (such as the epistatic interactions between groESL and a constellation of other genes) and preserve the differentiation of lineages, while others (such as the associations between capsular serotype and lineage) remain in continuous flux.

epidemiology↗