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Andrew Rambaut

Publications and source records attributed to Andrew Rambaut.

At least 19 recordsLinked to original sources
PubMed2026

Emergence of a Bundibugyo virus variant in the 2026 outbreak in the Democratic Republic of the Congo and Uganda.

In May 2026, an outbreak of Ebola disease caused by Bundibugyo virus (BDBV, species Orthoebolavirus bundibugyoense) was declared in the Democratic Republic of the Congo (DRC), with cases originating from DRC and locally transmitted cases reported in Uganda. Bundibugyo virus disease (BVD) outbreaks were previously recorded in 2007-2008 in Bundibugyo District, Uganda, and in 2012 in Isiro, DRC. Here, we generated 22 genomes from samples obtained from individuals with BVD in DRC and Uganda. These genomes form a well-supported phylogenetic cluster separate from BDBV variants associated with the 2007 and 2012 outbreaks, together with evidence for sustained human transmission. This is consistent with the emergence of a new zoonotic spillover event rather than resurgence from previously reported variants. Besides ongoing efforts in strengthening surveillance systems, community engagement, establishing Ebola treatment centers, and developing targeted medical countermeasures; our report advocates to specifically increase decentralized laboratory diagnostics capacity, with pan-Orthoebolavirus assays, including genomic sequencing capacity, for limiting further outbreak expansion, timely detection and control of future outbreaks.

Journal Article↗
PubMed2026

Deciphering the etiology of the 2024 outbreak of undiagnosed febrile illness in Panzi, Democratic Republic of the Congo.

In late 2024, an outbreak of over 400 cases of undiagnosed febrile illness, predominantly presenting as fever and cough, was reported in Panzi Health Zone, southwestern Democratic Republic of the Congo. Here we conducted an epidemiological and laboratory investigation to determine the etiology of the outbreak. Clinical data and specimens were prospectively collected from 108 individuals, of whom 59/108 (54.6%) were female. Children aged <5&#x2009;years were the most affected (47/108, 43.5%); 14/32 (43.7%) were malnourished. Oro/nasopharyngeal swabs from 96/108 individuals were PCR tested; 26 blood samples were sequenced. Plasmodium falciparum was detected in 56/108 (51.8%) individuals. Co-infections were also detected, with influenza A(H1N1)pdm09 virus in 16/56 (28.6%) and severe acute respiratory syndrome coronavirus 2 in 10/56 (17.9%) individuals. No novel pathogens were detected via metagenomics. Our findings suggest that the outbreak was primarily associated with a surge in malaria cases, with concurrent viral respiratory infections. Increasing decentralized laboratory capacity and strengthening broader health systems remain crucial for faster outbreak detection and investigation.

Disease Outbreaks↗
PubMed2025

Parallel algorithms for phylogenetic inference under a structured coalescent approximation.

While advances in molecular epidemiology and computational modeling have enhanced our capacity to track pathogen evolution, the accurate reconstruction of spatiotemporal transmission dynamics remains essential for developing epidemic preparedness frameworks and implementing outbreak response measures. Structured coalescent models offer a phylogeographic framework by restricting lineage coalescence events to geographically proximate host populations. Although the Bayesian structured coalescent approximation (BASTA) provides a tractable approach, contemporary phylogeographic analyses involving dozens of geographic localities and hundreds to thousands of viral genomes substantially exceed the computational capacity of existing implementations. The BASTA likelihood scales cubically with deme count and quadratically with sequence count due to matrix exponentiation and pairwise coalescent probability calculations. Here, we introduce a comprehensive algorithmic restructuring of the structured coalescent likelihood that eliminates redundancies, optimizes memory access, and exposes parallelization opportunities. Our approach reorganizes computations along three dimensions: (i) independent calculation of deme-transition probability matrices across time intervals; (ii) simultaneous evaluation of partial likelihood vectors within temporal slices; and (iii) concurrent aggregation of coalescent probabilities. Algorithmic restructuring cuts average coalescent likelihood computation by 7-8 fold, and parallelization further boosts performance to 10-26 fold, enabling joint phylogeographic analyses of dengue virus across 10 South American countries and H5N1 avian influenza across 20 Eurasian regions to finish in a fraction of prior time. This computational efficiency also enables comparison between backward-in-time structured coalescent approximations and forward-in-time phylogeographic methods, revealing that the former provides appropriately conservative posterior estimates, particularly at intermediate phylogenetic depths. We integrate our implementation into the popular BEAST X and BEAGLE software packages, with an accompanying interface in BEAUti X to easily set up the analyses, providing researchers with an accessible and scalable tool for real-time phylogeographic surveillance of rapidly evolving pathogens.

Journal Article↗
PubMed2025

Metagenomics reveals cryptic circulation of zoonotic viruses in Nigeria.

Zoonotic spillover events pose an ongoing threat to global health, with historic and recent viral diseases of international concern emerging from animal reservoirs 1-6. In Nigeria, limited surveillance of animal hosts at the human and animal interface continues to hinder our understanding of viruses that are cryptically circulating in animals near human dwellings with potential for consequential spillover events. We performed unbiased metagenomic next-generation sequencing (mNGS) on tissue and swab samples collected from 240 individual animals across 11 taxa (rodents, shrews, bats, goats, sheep, pigs, dogs, cats, chickens, cattle egrets, and lizards) in two Lassa-affected Nigerian states (Ondo and Ebonyi). Host-depleted sequencing reads were assembled into contigs, taxonomically classified, and subjected to phylogenetic analyses to characterize viral diversity, host associations, and evidence of cross-species transmission. Across all samples, we identified 214 distinct viral taxa spanning 33 families, of which 41% (n = 83) represent novel species by ICTV criteria. Positive-sense RNA viruses dominated (Coronaviridae, Picornaviridae, Astroviridae), followed by negative-sense RNA, single- and double-stranded DNA, and double-stranded RNA viruses. Notably, human-associated enteroviruses-including Hepatitis A virus (genotype 1b), echoviruses, coxsackieviruses, and noroviruses-were detected in goats, pigs, dogs, and chickens, indicating cryptic circulation of human pathogens in peridomestic and domesticated animals. Phylogenetic reconstructions revealed multiple cross-species viral sharing events, particularly among rodents, goats, sheep, and pigs, and extensive recombination within Nigerian Betacoronavirus 1 lineages. Interestingly we found a putative novel avian like coronavirus in rodents, goats and sheep. Ecological modelling demonstrated that host species identity, sample type, and sampling effort were primary drivers of viral richness and abundance, and that higher overall viral diversity strongly predicted cross-species transmission potential. Our integrated mNGS approach uncovered a rich and dynamic virome within animals inhabiting human-dominated environments in Nigeria, including undetected circulation of human enteric viruses. These findings underscore the importance of broad-taxonomic, real-time surveillance at human-animal interfaces to inform early-warning systems and pandemic preparedness, particularly in low-resource settings.

Journal Article↗
PubMed2025

Genomic epidemiology of clade Ia monkeypox viruses circulating in the Central African Republic in 2022-24: a retrospective cross-sectional study.

BACKGROUND: The spread of monkeypox virus (Orthopoxvirus monkeypox) clade Ib from the Democratic Republic of the Congo to neighbouring countries has raised global concerns, leading to WHO declaring mpox a public health emergency on Aug 14, 2024. We applied genomic epidemiology to investigate the causes of recurrent mpox outbreaks in the Central African Republic. We aimed to determine whether frequent zoonotic spillovers or increased human-to-human transmissions are driving mpox epidemiology. METHODS: We performed a retrospective cross-sectional study of monkeypox virus genomic sequences among PCR-confirmed mpox cases detected in the Central African Republic between Feb 17, 2022, and Sept 17, 2024. We used hybridisation capture coupled to high throughput sequencing to analyse 46 samples from mpox outbreaks that occurred in eight of the 20 prefectures (14 of 35 health districts). Near-complete genomes were used for phylogenomic analyses. FINDINGS: Between Jan 10, 2022, and Sept 15, 2024, 89 mpox cases were confirmed, including 53 cases in the first 9 months of 2024. We generated 41 near-complete genomes from this period, including 33 from 2024. All new and already published monkeypox virus genomes from the Central African Republic belonged to clade Ia. These genomes spanned the phylogenetic diversity of clade Ia viruses, and most likely represented several dozen independent transmission events to humans. The monkeypox virus phylogenetic diversity was geographically structured within the country. Plausibly linked cases often showed indistinguishable genomes. Conversely, we detected identical genomes in cases that epidemiological information would suggest were independent outbreaks. Finally, we found that three distinct viruses caused cases in the capital city of Bangui in July, 2024, with all three detected on the same day (July 24, 2024). We did not detect substantial enrichment of APOBEC3 editing, suggesting limited human-to-human transmission. INTERPRETATION: The data indicate that mpox epidemiology in the Central African Republic is primarily driven by short-lived outbreaks resulting from many independent zoonotic spillover events, particularly in rural areas. Although evidence remains limited, in Bangui additional factors such as movement of people and importation of bushmeat from other regions might be introducing the virus into urban settings. Similar spillover patterns have been observed in the Democratic Republic of the Congo. The poorly understood nature of monkeypox virus reservoirs in both countries is a regional concern, as frequent spillovers increase the risk of outbreaks leading to sustained human transmission. Beyond strengthening surveillance and developing countermeasures, it is important to better understand the reservoirs and focus on reducing transmission opportunities to prevent further outbreaks. FUNDING: Pasteur Institute of Bangui, Africa CDC, AFROSCREEN, WHO, the Helmholtz Institute for One Health, and the Deutsche Forschungsgemeinschaft.

Humans↗
PubMed2024

A framework for automated scalable designation of viral pathogen lineages from genomic data.

Pathogen lineage nomenclature systems are a key component of effective communication and collaboration for researchers and public health workers. Since February 2021, the Pango dynamic lineage nomenclature for SARS-CoV-2 has been sustained by crowdsourced lineage proposals as new isolates were sequenced. This approach is vulnerable to time-critical delays as well as regional and personal bias. Here we developed a simple heuristic approach for dividing phylogenetic trees into lineages, including the prioritization of key mutations or genes. Our implementation is efficient on extremely large phylogenetic trees consisting of millions of sequences and produces similar results to existing manually curated lineage designations when applied to SARS-CoV-2 and other viruses including chikungunya virus, Venezuelan equine encephalitis virus complex and Zika virus. This method offers a simple, automated and consistent approach to pathogen nomenclature that can assist researchers in developing and maintaining phylogeny-based classifications in the face of ever-increasing genomic datasets.

Animals↗
PubMed2007

Phylogenetic evidence for deleterious mutation load in RNA viruses and its contribution to viral evolution.

Populations of RNA viruses are often characterized by abundant genetic variation. However, the relative fitness of these mutations is largely unknown, although this information is central to our understanding of viral emergence, immune evasion, and drug resistance. Here we develop a phylogenetic method, based on the distribution of nonsynonymous and synonymous changes, to assess the relative fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals that a substantial proportion of the amino acid variation observed in natural populations of RNA viruses comprises transient deleterious mutations that are later purged by purifying selection, potentially limiting virus adaptability. We also demonstrate, for the first time, the existence of a relationship between amino acid variability and the phylogenetic distribution of polymorphisms. From this relationship, we propose an empirical threshold for the maximum viable deleterious mutation load in RNA viruses.

Amino Acid Sequence↗
PubMed2006

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

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.

Child↗
PubMed2006

Assessment of automated genotyping protocols as tools for surveillance of HIV-1 genetic diversity.

BACKGROUND: The routine use of drug resistance testing provides an abundant source of HIV-1 sequence data. However, it is not clear how reliable standard genotyping of these sequences is for describing HIV-1 genetic variation and for detecting novel genetic variants and epidemiological trends. OBJECTIVES: To compare assignment of HIV-1 resistance test sequences to reference strains across commonly used genotyping protocols. METHODS: Subtype assignments were compared across three standard genotyping protocols for 10 537 resistance test sequences, representing approximately one-fifth of all reported infections in the United Kingdom. Sequences that were inconsistently genotyped across methods, or that were unassigned by at least one method, were examined for evidence of recombination using sliding-window-based approaches. RESULTS: Although agreement across methods was high for subtypes B, C and H, it was generally much lower (< 50%) for other subtypes. Disagreement between methods typically involved closely related, but epidemiologically distinct, groups or involved a significant proportion ( approximately 12%) of divergent sequences in which analysis revealed widespread evidence of recombination and a remarkable diversity of unusual recombinant forms. CONCLUSIONS: With frequent long-distance transfer of viral strains and widespread recombination between them, genetic and epidemiological relationships within HIV-1 are becoming increasingly complex. Current methods of subtype assignment vary in their ability to identify novel genetic variants and to distinguish epidemiologically distinct strains. Capturing meaningful epidemiological information from resistance test data will require a critical understanding of the methodologies used in order to appreciate the possible sources of error and misclassification.

Databases, Genetic↗
PubMed2006

A phylogenetic method for detecting positive epistasis in gene sequences and its application to RNA virus evolution.

RNA virus genomes are compact, often containing multiple overlapping reading frames and functional secondary structure. Consequently, it is thought that evolutionary interactions between nucleotide sites are commonplace in the genomes of these infectious agents. However, the role of epistasis in natural populations of RNA viruses remains unclear. To investigate the pervasiveness of epistasis in RNA viruses, we used a parsimony-based computational method to identify pairs of co-occurring mutations along phylogenies of 177 RNA virus genes. This analysis revealed widespread evidence for positive epistatic interactions at both synonymous and nonsynonymous nucleotide sites and in both clonal and recombining viruses, with the majority of these interactions spanning very short sequence regions. These findings have important implications for understanding the key aspects of RNA virus evolution, including the dynamics of adaptation. Additionally, many comparative analyses that utilize the phylogenetic relationships among gene sequences assume that mutations represent independent, uncorrelated events. Our results show that this assumption may often be invalid.

DNA Mutational Analysis↗
PubMed2006

Relaxed phylogenetics and dating with confidence.

In phylogenetics, the unrooted model of phylogeny and the strict molecular clock model are two extremes of a continuum. Despite their dominance in phylogenetic inference, it is evident that both are biologically unrealistic and that the real evolutionary process lies between these two extremes. Fortunately, intermediate models employing relaxed molecular clocks have been described. These models open the gate to a new field of "relaxed phylogenetics." Here we introduce a new approach to performing relaxed phylogenetic analysis. We describe how it can be used to estimate phylogenies and divergence times in the face of uncertainty in evolutionary rates and calibration times. Our approach also provides a means for measuring the clocklikeness of datasets and comparing this measure between different genes and phylogenies. We find no significant rate autocorrelation among branches in three large datasets, suggesting that autocorrelated models are not necessarily suitable for these data. In addition, we place these datasets on the continuum of clocklikeness between a strict molecular clock and the alternative unrooted extreme. Finally, we present analyses of 102 bacterial, 106 yeast, 61 plant, 99 metazoan, and 500 primate alignments. From these we conclude that our method is phylogenetically more accurate and precise than the traditional unrooted model while adding the ability to infer a timescale to evolution.

Animals↗
PubMed2006

Longitudinal population analysis of dual infection with recombination in two strains of HIV type 1 subtype B in an individual from a Phase 3 HIV vaccine efficacy trial.

This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development.

AIDS Vaccines↗
PubMed2006

JC virus evolution and its association with human populations.

The ubiquitous human polyomavirus JC (JCV) is a small double-stranded DNA virus that establishes a persistent infection, and it is often transmitted from parents to children. There are at least 14 subtypes of the virus associated with different human populations. Because of its presumed codivergence with humans, JCV has been used as a genetic marker for human evolution and migration. Codivergence has also been used as a basis for estimating the rate of nucleotide substitution in JCV. We tested the hypothesis of host-virus codivergence by (i) performing a reconciliation analysis of phylogenetic trees of human and JCV populations and (ii) providing the first estimate of the evolutionary rate of JCV that is independent from the assumption of codivergence. Strikingly, our comparisons of JCV and human phylogenies provided no evidence for codivergence, suggesting that this virus should not be used as a marker for human population history. Further, while the estimated nucleotide substitution rate of JCV has large confidence intervals due to limited sampling, our analysis suggests that this virus may evolve nearly two orders of magnitude faster than predicted under the codivergence hypothesis.

DNA, Mitochondrial↗
PubMed2006

Phylogenetic analysis reveals a correlation between the expansion of very virulent infectious bursal disease virus and reassortment of its genome segment B.

Infectious bursal disease virus (IBDV) is a birnavirus causing immunosuppressive disease in chickens. Emergence of the very virulent form of IBDV (vvIBDV) in the late 1980s dramatically changed the epidemiology of the disease. In this study, we investigated the phylogenetic origins of its genome segments and estimated the time of emergence of their most recent common ancestors. Moreover, with recently developed coalescence techniques, we reconstructed the past population dynamics of vvIBDV and timed the onset of its expansion to the late 1980s. Our analysis suggests that genome segment A of vvIBDV emerged at least 20 years before its expansion, which argues against the hypothesis that mutation of genome segment A is the major contributing factor in the emergence and expansion of vvIBDV. Alternatively, the phylogeny of genome segment B suggests a possible reassortment event estimated to have taken place around the mid-1980s, which seems to coincide with its expansion within approximately 5 years. We therefore hypothesize that the reassortment of genome segment B initiated vvIBDV expansion in the late 1980s, possibly by enhancing the virulence of the virus synergistically with its existing genome segment A. This report reveals the possible mechanisms leading to the emergence and expansion of vvIBDV, which would certainly provide insights into the scope of surveillance and prevention efforts regarding the disease.

Animals↗
PubMed2005

Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences.

Although phylogenetic inference of protein-coding sequences continues to dominate the literature, few analyses incorporate evolutionary models that consider the genetic code. This problem is exacerbated by the exclusion of codon-based models from commonly employed model selection techniques, presumably due to the computational cost associated with codon models. We investigated an efficient alternative to standard nucleotide substitution models, in which codon position (CP) is incorporated into the model. We determined the most appropriate model for alignments of 177 RNA virus genes and 106 yeast genes, using 11 substitution models including one codon model and four CP models. The majority of analyzed gene alignments are best described by CP substitution models, rather than by standard nucleotide models, and without the computational cost of full codon models. These results have significant implications for phylogenetic inference of coding sequences as they make it clear that substitution models incorporating CPs not only are a computationally realistic alternative to standard models but may also frequently be statistically superior.

Classification↗
PubMed2005

Heterotachy and tree building: a case study with plastids and eubacteria.

The nature of heterotachy at the center of recent controversy over the relative performance of tree-building methods is different from the form of heterotachy that has been inferred in empirical studies. The latter have suggested that proportions of variable sites (p(var)) vary among orthologues and among paralogues. However, the strength of this inference, describing what may be one of the most important evolutionary properties of sequence data, has remained weak. Consequently, other models of sequence evolution have been proposed to explain some long-branch attraction (LBA) problems that could be attributed to differences in p(var). For an empirical case with plastid and eubacterial RNA polymerase sequences, we confirm using capture-recapture estimates and simulations that p(var) can differ among orthologues in anciently diverged evolutionary lineages. We find that parsimony and a least squares distance method that implements an overly simple model of sequence evolution are susceptible to LBA induced by this form of heterotachy. Although homogeneous maximum likelihood inference was found to be robust to model misspecification in our specific example, we caution against assuming that it will always be so.

Bacteria↗