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Incorporating Epidemiological Data into the Genomic Analysis of Partially Sampled Infectious Disease Outbreaks.

Pathogen genomic data are increasingly being used to investigate transmission dynamics in infectious disease outbreaks. Combining genomic data with epidemiological data should substantially increase our understanding of outbreaks, but this is highly challenging when the outbreak under study is only partially sampled, so that both genomic and epidemiological data are missing for intermediate links in the transmission chains. Here, we present a new dynamic programming algorithm to perform this task efficiently. We implement this methodology into the well-established TransPhylo framework to reconstruct partially sampled outbreaks using a combination of genomic and epidemiological data. We use simulated datasets to show that including epidemiological data can improve the accuracy of the inferred transmission links compared with inference based on genomic data only. This also allows us to estimate parameters specific to the epidemiological data (such as transmission rates between particular groups), which would otherwise not be possible. We then apply these methods to two real-world examples. First, we use genomic data from an outbreak of tuberculosis in Argentina, for which data was also available on the HIV status of sampled individuals, in order to investigate the role of HIV coinfection in the spread of this tuberculosis outbreak. Second, we use genomic and geographical data from the 2003 epidemic of avian influenza H7N7 in the Netherlands to reconstruct its spatial epidemiology. In both cases, we show that incorporating epidemiological data into the genomic analysis allows us to investigate the role of epidemiological properties in the spread of infectious diseases.

Humans

Temporal reconstruction of a Salmonella Enteritidis ST11 outbreak in New Zealand.

Outbreaks caused by Salmonella Enteritidis are commonly linked to eggs and poultry meat internationally, but this serovar had never been detected in Aotearoa New Zealand (NZ) poultry prior to 2021. Locally designated genomic cluster Salmonella Enteritidis_2019_C_01, was implicated in a 2019 outbreak associated with a restaurant in Auckland. Four Enteritidis_2019_C_01 sub-clusters have since been identified, two retrospectively, in the Auckland region. Authorities initiated a formal outbreak investigation after genomically indistinguishable S. Enteritidis was isolated from the NZ poultry production environment. This study analysed 231 S. Enteritidis genomes obtained from the outbreak using Bayesian phylodynamic tools to gain insight into the outbreak's dynamics and origin. We used Bayesian integrated coalescent epoch plots to estimate the change of the Enteritidis ST11 population size over time and marginal structured coalescent approximation to estimate transmission between poultry producers. We investigated human and poultry isolates to elucidate the time and location of the most recent common ancestor of the outbreak and transmission pathways. The median most recent common ancestor was estimated to be February 2019. We found evidence of amplification and spread of strain Enteritidis_2019_C_01 within the poultry industry, as well as transmission events throughout the production chain. The intervention by the public health and food safety authorities coincided with a drop in the effective population size of the S. Enteritidis ST11 as well as notified human cases. This information is crucial for understanding and preventing the transmission of S. Enteritidis in NZ poultry to ensure poultry meat and eggs are safe for consumption.

Salmonella enteritidis

Detection of Serratia outbreaks in hospital.

Infections due to Serratia marcescens were studied in 23 different hospitals. A retrospective study was done in 4 hospitals; all isolates were compared by serological typing, antibiograms, bacteriocin production, and bacteriocin sensitivity. 2 of the hospitals were having cross-infection problems due to antibiotic-resistant strains, but the other 2 had little or no cross-infection. Outbreaks were studied in 19 other hospitals. 9 of these outbreaks were classified as "common source" since contaminated "sterile solutions" were incriminated as the cause in each. One hospital had a "pseudo-outbreak," in which Serratia from E.D.T.A. blood-collecting tubes contaminated blood-cultures as they were collected. All 10 of these strains from common-source outbreaks were generally sensitive to antibiotics. Outbreaks in 9 other hospitals resulted from cross-infection and were caused by strains which were very resistant to antibiotics. Guidelines for detecting outbreaks are given and control measures are suggested.

Alabama

Interspecies Exchange of Mobile Genetic Elements During a Plant Disease Outbreak.

Outbreak sequencing provides insight into the origin and evolutionary processes acting on emerging pathogens. Sequencing a historic multihost outbreak of Ralstonia spp. in Martinique shows the outbreak was caused by two lineages that diverged at separate times from mainland populations. One lineage (Ralstonia pseudosolanacearum I-18) was originally introduced from Asia to South America, where it became well established prior to its dissemination to Martinique, where it retains a signature of specialization on solanaceous hosts. The novel lineage first identified during the outbreak (Ralstonia solanacearum IIB-4NPB) arose from a mainland population endemic to the Americas prior to its arrival in Martinique, where host-range expansion was observed. In contrast to minor changes in secreted effector protein repertoires, the emergent R. solanacearum IIB-4NPB acquired a novel integrative and conjugative element (ICERsoRUN1145). After identifying all Ralstonia spp. ICEs and mapping their spatial and phylogenetic distribution among Ralstonia spp. sampled during the outbreak, we found closely related ICEs circulating in mainland populations of R. pseudosolanacearum, indicating likely exchange between introduced and endemic Ralstonia spp. The family of ICEs in Ralstonia (ICERs) has a conserved bipartite structure and display a striking pattern of functional specialization in each cargo gene insertion hotspot: the first hotspot is a target for metabolic gene acquisition, and the second is a target for defense element acquisition. This work provides unparalleled phylogenetic and spatial resolution of an unusual outbreak and highlights the role of horizontal transfer in shaping the ecological success of an emerging pathogen.

Plant Diseases

Comparison of ribotyping and restriction enzyme analysis using pulsed-field gel electrophoresis for distinguishing Legionella pneumophila isolates obtained during a nosocomial outbreak.

Because of the ubiquity of Legionella isolates in aquatic habitats, epidemiologic evaluation of Legionella pneumophila strains is important in the investigation and subsequent control of nosocomial outbreaks of legionellosis. In this study, ribotyping and restriction enzyme analysis by pulsed-field gel electrophoresis (PFGE) were used to compare isolates of L. pneumophila obtained from patients and the environment during a nosocomial outbreak with unrelated control strains. Restriction enzyme analysis by PFGE resolved 14 different patterns among the L. pneumophila serogroup 1 and L. pneumophila serogroup 6 isolates involved in the study. Two of the patterns were observed in the three L. pneumophila serogroup 6 isolates from patients with confirmed nosocomial infections and environmental isolates from the potable water supply, which was, therefore, believed to be the source of the patients' infections. Three more patterns that were not present in isolates from patients with legionellosis were seen in isolates from the hospital environment, demonstrating the presence of multiple strains in the hospital environment. In the outbreak, one distinct pattern occurred among the L. pneumophila serogroup 1 isolates from patients with nosocomial infections, suggesting a common source; however, the source could not be determined. By comparison, ribotyping generated five patterns. However, some control strains of both L. pneumophila serogroups 1 and 6 possessed the same ribotypes as were present in the outbreak isolates. Both techniques were used successfully to subtype the isolates obtained during the investigation of the outbreak. Furthermore, restriction enzyme analysis by PFGE was useful for subdividing ribotypes and for distinguishing strains involved in the outbreak from epidemiologically unrelated strains.

Adult

A multistate outbreak of Salmonella javiana and Salmonella oranienburg infections due to consumption of contaminated cheese.

OBJECTIVE: To determine the source of an outbreak of Salmonella javiana and Salmonella oranienburg infections. DESIGN: Laboratory-based statewide surveillance for Salmonella infections and two separate case-control studies. SETTING: Community- and industry-based studies conducted from May through October 1989. PARTICIPANTS: Thirty-one culture-confirmed outbreak-associated cases of S javiana infection and 60 community controls matched for telephone prefix, gender, and age in case-control study I; 50 cases, 100 community controls, and 64 family member controls in case-control study II. RESULTS: One hundred thirty-six culture-confirmed cases of S javiana infection and 11 cases of S oranienburg infection were associated with the outbreak in Minnesota. Outbreak-associated cases were also identified in Wisconsin (15 cases), and in Michigan and New York (one case each). Cases were more likely than controls to have consumed mozzarella cheese manufactured at a single cheese plant (plant X) or cheese that had been shredded at processing plants that also shredded cheese manufactured at plant X (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.7 to 23.2; P < .01). The outbreak-associated strains of both serovars were isolated from two unopened 16-oz (0.45-kg) blocks of mozzarella cheese produced at plant X. The most probable numbers of Salmonella organisms in these samples were 0.36/100 g and 4.3/100 g. CONCLUSIONS: The potential for bacterial pathogen contamination of cheese during manufacture and processing has important epidemiologic implications, particularly because cheese consumption has recently increased in the United States. Low-level contamination of a nationally distributed food product can cause geographically dispersed foodborne outbreaks that may be difficult to detect.

Adolescent

Epidemiology of common-source outbreaks of shigellosis in the United States, 1961-1975.

In 1961-1975, there were 72 foodborne and 38 waterborne outbreaks of shigellosis reported in the United States. Foodborne outbreaks were most often caused by salads with contamination attributed to poor hygiene of a food handler. Waterborne outbreaks most often involved semipublic water systems, and were usually the result of inadequate chlorination of water contaminated by human feces. In 110 common-source outbreaks, 16,541 persons were ill. The attack rate for both food- and waterborne shigellosis was 47%, and the case-fatality ratio was 0.1% in foodborne outbreaks and 0.2% in waterborne outbreaks.

Disease Outbreaks

[Dimorphous Hansen's disease with outbreaks of Hansen reactions and visceral lesions].

The paper presents the case of a patient with borderline hanseniasis. After a long period of illness, he presented an outbreak with new lesions, that showed reactional tuberculoid aspects; he later presented lesions with clinical and histological aspects of Virchowian hanseniasis. This evolutional type is compatible with the pseudo-exacerbations outbreaks reported by Souza Lima. This patient also presented an Erythema Nodosum outbreak with cutaneous and visceral lesions, the latter occurring with great intensity in the liver parenchyma with clinical manifestations of icterus and hepatomegaly. The pathogenesis of the pseudo-exacerbations outbreaks is discussed, also the special situation of Borderline patients, subject to neurologic injuries during the pseudo-exacerbations outbreaks, and cutaneous, neurological and visceral lesions during the Erythema Nodosum Hansenicum outbreaks.

Erythema Nodosum

Costs of an outbreak of wound infections in an orthopaedic ward.

An outbreak of serious wound infections occurring in an orthopaedic ward is reported. The outbreak involved 10 patients, all of whom had undergone clean, orthopaedic operative procedures. The outbreak was eventually terminated by discarding five damaged and contaminated mattresses. The costs incurred during this outbreak were calculated using a retrospective comparative study. The infected patients had an average increased hospital stay of 17 days and average increased costs of 2220 pounds. The outbreak demonstrated the high costs of hospital-acquired infection and the need for further investment in infection control programmes.

Beds

Genomic characteristics and tracing analysis of an acute gastroenteritis outbreak associated with rotavirus C in a boarding high school.

BACKGROUND: Rotaviruses are major pathogens of childhood acute gastroenteritis, dominated by rotavirus A (RVA). Outbreaks caused by human rotavirus C (RVC) are rarely reported, and relevant genomic data remain scarce. This genomic investigation of an RVC outbreak improves our understanding of viral diversity and transmission dynamics. METHODS: We performed epidemiological surveys, nucleic acid testing and whole-genome sequencing (WGS) on specimens from a 2025 RVC-associated gastroenteritis outbreak at a Chinese boarding high school. Sequence alignment, phylogenetic and molecular tracing analyses were conducted to explore RVC evolution via point mutation, segment reassortment and genomic recombination. RESULTS: This typical point-source campus outbreak was linked to an indoor student gathering matching the incubation period of RVC. Thirteen RVC FX strains were recovered from 11 rectal swabs and two vomitus samples. Their viral protein (VP) 4 and VP7 sequences shared high homology with Russian reference strains, carrying distinct amino acid variations. No segment reassortment or recombination was detected in VP4/VP7 genes. CONCLUSIONS: Dense, closed campus settings facilitate RVC clustered transmission. Limitations included absent screening of asymptomatic canteen staff. Rapid nucleic acid testing enabled timely pathogen identification for outbreak control. Greater attention should be paid to the public health risk of RVC. These whole-genome sequencing data enrich resources for studying RVC evolution and vaccine development.

Acute gastroenteritis outbreak

Measles: lessons from an outbreak.

BACKGROUND: Measles outbreaks continue to be a problem for infection control in hospitals--patients, personnel, and employee health service. Guidelines for measles outbreaks are not clear for medical personnel in the hospital. METHODS: Outbreak investigation in a university-affiliated teaching hospital. RESULTS: Four primary cases resulted in 607 staff exposures and two secondary cases. Forty-seven medical personnel were furloughed and 88 were vaccinated for measles. Minimal serologic criteria for immunity were found to be inadequate in the outbreak setting. CONCLUSIONS: We found that serologic guidelines for assessing immunity to measles are inadequate. During the outbreak, we arbitrarily doubled the acceptable enzyme-linked immunosorbent assay titers that we would consider protective, > or = 2, to decrease the possibility of further secondary cases. Employees with enzyme-linked immunosorbent assay measles titers less than 2 and without a definite history of natural measles were revaccinated with a measles vaccine. This strategy takes advantage of the anamnestic response that revaccination would confer in persons with low antibody titer.

Adult

Investigation of a Mycobacterium fortuitum prosthetic joint infection outbreak at two ambulatory surgery centers in Tennessee.

OBJECTIVE: This study outlines the investigation into an outbreak of Mycobacterium fortuitum infections involving 17 cases undergoing hip or knee surgeries at two ambulatory surgery centers (ASCs) in Tennessee from January 2023 to November 2024. Notably, the outbreak could not be attributed to contaminated water sources, which are typically associated with non-tuberculous mycobacteria (NTM) outbreaks, presenting a unique challenge. METHODS: Outbreak investigation steps included Infection Prevention (IP) assessments, case-control study, environmental sampling, whole genome sequencing, and a healthcare personnel (HCP) exposure questionnaire. RESULTS: IP assessment highlighted several concerns, including no formal facility water management program (WMP), a lack of dedicated IP personnel and certified sterile processing staff, the absence of a formalized system for tracking surgical site infections, and a notable gap in understanding the requirements for reporting diseases. The case-control findings revealed a significant association between the presence of a surgical technologist in the operating room during the procedures and the occurrence of NTM infections, indicated by an odds ratio of 55.77 (95% CI [3.16-985.44]; P = 0.0097). Thirteen clinical isolates collected at one ASC and three additional isolates collected at a second ASC were highly related by whole genome sequencing. CONCLUSION: The study further elucidates valuable insights gained from the outbreak response, including the gaps in surveillance within the ambulatory surgical setting and systematic collection of cultures from environmental sources. It emphasizes the importance of thorough vetting, onboarding, continuing education, and practice monitoring for HCP.

Humans

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

Nosocomial Outbreak of Lassa Fever in Conakry, Guinea, 2022.

BACKGROUND: Lassa fever is endemic in Guinea, with high seroprevalence in the forest region. However, clinical cases have been only anecdotally reported. In August 2022, a nosocomial outbreak occurred at a private clinic in the capital, Conakry, an area previously considered low risk. METHODS: Suspected cases were confirmed by real-time reverse-transcription polymerase chain reaction within 24 hours. Viremia was monitored during hospitalization, and whole-genome sequencing was performed in-country within 13 days of outbreak detection. Outbreak investigation involved rodent testing in the home village of the suspected primary case. RESULTS: Six cases were laboratory-confirmed, 5 of which were healthcare workers of the clinic. The case fatality rate was 16.7%. Viral RNA remained detectable in blood of survivors for a median of 26 days (interquartile range, 24-41 days) post-disease onset. Epidemiological investigations identified a suspected primary case, who had died of a febrile disease compatible with Lassa fever, had contact with all secondary cases, and had a travel history from Kissidougou area. Three near-complete and 1 partial Lassa virus genomes were recovered from the secondary cases, which phylogenetically clustered with genomes from central Guinea. Consistent with a common transmission source, the 4 genomes were almost identical. Rodent testing revealed a new reservoir area in eastern-central Guinea. CONCLUSIONS: This outbreak highlights the vulnerability of healthcare settings in low-prevalence areas of West Africa to nosocomial Lassa virus transmission due to human mobility. Facilitated by capacity-building programs for viral hemorrhagic fevers, rapid diagnosis, genomic analysis, and ecological assessment enabled an efficient outbreak response and control.

Lassa Fever

Use of ribosomal RNA gene restriction patterns to investigate two outbreaks of Campylobacter enteritis in Melbourne, Australia.

The analysis of ribosomal RNA (rRNA) gene patterns (ribotyping) has been used to differentiate strains within bacterial species. We used this method to investigate two outbreaks of campylobacter enteritis that occurred recently in Melbourne, Australia. The first outbreak involved seven patients although isolates from only five patients were available for typing. The second outbreak consisted of three patients infected with human immunodeficiency virus (HIV) on the same ward of a hospital. Analysis of the rRNA gene patterns revealed identical patterns for the isolates from five patients in the first outbreak, suggesting that these isolates were from the same source. However, ribotyping of the four isolates from the second outbreak showed three distinct ribotypes indicative of contact with unrelated sources. This study demonstrated that ribotyping is a useful, reliable and convenient typing scheme for epidemiological purposes.

Australia

Early outbreaks of 'epidemic neuromyasthenia'.

The literature of the outbreaks of 'epidemic neuromyasthenia' (ENM) from 1934 to 1955 has been selected to show that the disease affects other people besides young adult females in hospitals and nursing homes. There have been district epidemics, in which the male: female ratio was almost even and several male outbreaks affecting soldiers in barracks. Some outbreaks appear to have been triggered off by an epidemic of poliomyelitis, and the epidemiology of outbreaks in Iceland in 1948 and 1955 suggests that the normal cytopathological effects of poliomyelitis infection have been suppressed by the new disease. In the Durban epidemic (1955) a toxic metabolite was discovered in the urine of many patients and a markedly increased urinary excretion of creatine was noted in two New York State outbreaks. The results of the transmission of an agent from patients with ENM to monkeys suggest that the neurological disorder might be in the form of mild disseminated lesions scattered throughout the nervous system from the brain to peripheral nerves and associated with perivascular round cell infiltration without significant cellular damage. ENM infection was widespread in the North of England in 1955 and associated with lymphocyte abnormalities, which have persisted in some cases for several years. This suggests a continuous organic process.

Australia

Theoretical epidemiology on bovine ephemeral fever outbreaks in Tanegashima Island, Kagoshima Prefecture of Japan in 1988.

From the end of September to November 1988, a compact scale of bovine ephemeral fever (BEF) outbreaks occurred suddenly in Tanegashima island of Kagoshima Prefecture, southern part of Kyusyu island of Japan. The BEF outbreak pattern showed epidemical characteristics as follows; (1) outbreak spread from few foci to zone during one month, and (2) the disease might be transmitted in farms with a fixed probability of adequate contact. By using the above aspects, we attempted to analyze the disease theoretically with the application of Poisson distribution and Reed-Frost model. The BEF incidence in farms was in well accord with the Poisson distribution. As the very rare event occurred in unit time or in unit area in this epidemic, the cattle population at risk were equivalently susceptible to BEF virus in this island, due to the influence of no vaccination to BEF control before the first outbreak. Similarly, the epidemic curve of the Reed-Frost model was proved to fit well the incidence observed in a farm, and the probability of adequate contact was induced as p = 0.226. If the cattle population is less than 5 in this farm, the outbreak would not occur in the first instance.

Animals

Outbreaks of fluconazole-resistant Candida parapsilosis are driven by low-biofilm-producing isolates that emerge under host selection.

Candida parapsilosis is a major human fungal pathogen, with recent global outbreaks driven by fluconazole-resistant (FLCR-Cp) isolates that are difficult to eradicate and associated with poor clinical outcomes. However, the microbial traits enabling persistence of these outbreak lineages remain poorly defined. Here, we show that FLCR-Cp isolates responsible for prolonged, multi-country outbreaks consistently exhibit a striking low-biofilm-producing (LBP) phenotype. Contrary to the prevailing view that robust biofilm formation promotes persistence, LBP strains displayed enhanced stress tolerance, increased cell wall masking, and reduced immune recognition. These traits conferred resistance to neutrophil and macrophage killing and enhanced survival in immune cell-rich organs during systemic infection. Genome-wide transcriptomic profiling revealed extensive metabolic and regulatory rewiring in LBP strains. Whole-genome sequencing (WGS) of a global isolate collection further demonstrated that the LBP phenotype has emerged independently multiple times, supporting convergent evolution under host selection. Functional genomic analyses suggest that biofilm attenuation arises through multigenic changes, and disruption of key biofilm-associated transcriptional regulators enhanced fitness during immune interactions. Together, our findings overturn the assumption that robust biofilm formation drives outbreak persistence and instead identify biofilm attenuation as an adaptive tradeoff that promotes immune evasion and long-term survival. These results redefine our understanding of C. parapsilosis adaptation during healthcare-associated outbreaks and shift attention toward host-driven evolutionary processes than environmental persistence alone.

Biofilms