Marburg virus disease outbreaks, mathematical models, and disease parameters: a systematic review.

The 2023 Marburg virus disease outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this lethal pathogen. We did a systematic review (PROSPERO CRD42023393345) of peer-reviewed articles reporting historical outbreaks, modelling studies, and epidemiological parameters focused on Marburg virus disease. We searched PubMed and Web of Science from database inception to March 31, 2023. Two reviewers evaluated all titles and abstracts with consensus-based decision making. To ensure agreement, 13 (31%) of 42 studies were double-extracted and a custom-designed quality assessment questionnaire was used for risk of bias assessment. We present detailed information on 478 reported cases and 385 deaths from Marburg virus disease. Analysis of historical outbreaks and seroprevalence estimates suggests the possibility of undetected Marburg virus disease outbreaks, asymptomatic transmission, or cross-reactivity with other pathogens, or a combination of these. Only one study presented a mathematical model of Marburg virus transmission. We estimate an unadjusted, pooled total random effect case fatality ratio of 61·9% (95% CI 38·8-80·6; I2=93%). We identify epidemiological parameters relating to transmission and natural history, for which there are few estimates. This systematic review and the accompanying database provide a comprehensive overview of Marburg virus disease epidemiology and identify key knowledge gaps, contributing crucial information for mathematical models to support future Marburg virus disease epidemic responses.

Comparing the transmission potential from sequence and surveillance data of 2009 North American influenza pandemic waves.

Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics. In this study, we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data. The impact of the choice of tree-priors, informative epidemiological priors, and evolutionary parameters on the transmission potential estimation is evaluated. North American Influenza A(H1N1)pdm09 hemagglutinin (HA) gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number (R 0 ). Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models. Path-sampling marginal likelihood estimation is conducted to assess model fit. A bibliographic search to gather surveillance-based R 0 values were consistently lower (mean ≤ 1.2) when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness (mean ≥ 1.3 to ≤2.88 days). The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates. While there was no certain impact of clock rate and tree height on the R 0 estimation, an opposite relationship was observed between coalescent and birth-death tree priors. There was no significant difference (p = 0.46) between the birth-death model and surveillance R 0 estimates. This study concludes that tree-prior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters. The study also reports a consensus between the sequence-based R 0 estimation and surveillance-based R 0 estimates. Altogether, these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess and respond to emerging infectious diseases.

Hospitalizations for COVID-19 Among American Indian and Alaska Native Adults (≥ 18 Years Old) - New Mexico, March-September 2020.

To assess the presence of racial disparity during the COVID-19 pandemic, the New Mexico Department of Health (NMDOH) sought to compare the case rate and risk of hospitalization between persons of American Indian and Alaska Native (AI/AN) race and persons of other races in New Mexico from March 1 through September 30, 2020. Using NMDOH COVID-19 surveillance data, age-standardized COVID-19 case and hospitalization risks were compared between adults (≥ 18 years old) of AI/AN and other races. We compared age, sex, and comorbidities between hospitalized adults of AI/AN and other races. Among AI/AN persons, age-standardized COVID-19 case and hospitalization risks were 3.7 (95% CI 3.6-3.8) and 10.5 (95% CI 9.8-11.2) times as high as persons of other races. Hospitalized AI/AN patients had higher proportions of diabetes mellitus (48% vs. 33%, P < 0.0001) and chronic liver disease (8% vs. 5%, P = 0.0004) compared to hospitalized patients of other races. AI/AN populations have disproportionately higher risk of COVID-19 hospitalization compared to other races in New Mexico. By identifying etiologic factors that contribute to inequity, public health partners can implement culturally appropriate health interventions to mitigate disease severity within AI/AN communities.

Host diversity and behavior determine patterns of interspecies transmission and geographic diffusion of avian influenza A subtypes among North American wild reservoir species.

Wild birds can carry avian influenza viruses (AIV), including those with pandemic or panzootic potential, long distances. Even though AIV has a broad host range, few studies account for host diversity when estimating AIV spread. We analyzed AIV genomic sequences from North American wild birds, including 303 newly sequenced isolates, to estimate interspecies and geographic viral transition patterns among multiple co-circulating subtypes. Our results show high transition rates within Anseriformes and Charadriiformes, but limited transitions between these orders. Patterns of transition between species were positively associated with breeding habitat range overlap, and negatively associated with host genetic distance. Distance between regions (negative correlation) and summer temperature at origin (positive correlation) were strong predictors of transition between locations. Taken together, this study demonstrates that host diversity and ecology can determine evolutionary processes that underlie AIV natural history and spread. Understanding these processes can provide important insights for effective control of AIV.

Characteristics of Persons With Secondary Detection of Severe Acute Respiratory Syndrome Coronavirus 2 ≥90 days After First Detection, New Mexico 2020.

The New Mexico Department of Health (NMDOH) conducted a matched case-control study to compare 315 persons (cases) with and 945 persons (controls) without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) secondary detection (ie, positive SARS-CoV-2 test ≥90 days after first detection as of December 10, 2020). Compared with controls, cases had greater odds of higher SARS-CoV-2 testing frequency (adjusted odds ratio [aOR] = 1.2), being female (aOR = 1.6), being non-Hispanic American Indian/Alaska Native (aOR = 2.3), having diabetes mellitus (aOR = 1.8), and residing and/or working in detention and/or correctional facilities (aOR = 4.7). Diagnostic tools evaluating infectiousness at secondary detection are urgently needed to inform infection control practices.

Methodological synthesis of Bayesian phylodynamics, HIV-TRACE, and GEE: HIV-1 transmission epidemiology in a racially/ethnically diverse Southern U.S. context.

This study introduces an innovative methodological approach to identify potential drivers of structuring HIV-1 transmission clustering patterns between different subpopulations in the culturally and racially/ethnically diverse context of Houston, TX, the largest city in the Southern United States. Using 6332 HIV-1 pol sequences from persons newly diagnosed with HIV during the period 2010-2018, we reconstructed HIV-1 transmission clusters, using the HIV-TRAnsmission Cluster Engine (HIV-TRACE); inferred demographic and risk parameters on HIV-1 transmission dynamics by jointly estimating viral transmission rates across racial/ethnic, age, and transmission risk groups; and modeled the degree of network connectivity by using generalized estimating equations (GEE). Our results indicate that Hispanics/Latinos are most vulnerable to the structure of transmission clusters and serve as a bridge population, acting as recipients of transmissions from Whites (3.0 state changes/year) and from Blacks (2.6 state changes/year) as well as sources of transmissions to Whites (1.8 state changes/year) and to Blacks (1.2 state changes/year). There were high rates of transmission and high network connectivity between younger and older Hispanics/Latinos as well as between younger and older Blacks. Prevention and intervention efforts are needed for transmission clusters that involve younger racial/ethnic minorities, in particular Hispanic/Latino youth, to reduce onward transmission of HIV in Houston.

Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak.

The 2014-2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.

Comparative Virological and Pathogenic Characteristics of Avian Influenza H5N8 Viruses Detected in Wild Birds and Domestic Poultry in Egypt during the Winter of 2016/2017.

The surveillance and virological characterization of H5N8 avian influenza viruses are important in order to assess their zoonotic potential. The genetic analyses of the Egyptian H5N8 viruses isolated through active surveillance in wild birds and domestic poultry in the winter of 2016/2017 showed multiple introductions of reassortant viruses. In this study, we investigated and compared the growth kinetics, infectivity, and pathogenicity of the three reassortant forms of H5N8 viruses detected in wild birds and domestic poultry in Egypt during the first introduction wave in the winter of 2016/2017. Three representative H5N8 viruses (abbreviated as 813, 871, and 13666) were selected. The 871/H5N8 virus showed enhanced growth properties in vitro in Madin Darby canine kidney (MDCK) and A549 cells. Interestingly, all viruses replicated well in mice without prior adaptation. Infected C57BL/6 mice showed 20% mortality for 813/H5N8 and 60% mortality for 871/H5N8 and 13666/H5N8, which could be attributed to the genetic differences among the viruses. Studies on the pathogenicity in experimentally infected ducks revealed a range of pathogenic effects, with mortality rate ranging from 0% for 813/H5N8 and 13666/H5N8 to 28% for 871/H5N8. No significant differences were observed among the three compared viruses in infected chickens. Overall, different H5N8 viruses had variable biological characteristics, indicating a continuous need for surveillance and virus characterization efforts.

Active surveillance and genetic evolution of avian influenza viruses in Egypt, 2016-2018.

Egypt is a hotspot for avian influenza virus (AIV) due to the endemicity of H5N1 and H9N2 viruses. AIVs were isolated from 329 samples collected in 2016-2018; 48% were H9N2, 37.1% were H5N8, 7.6% were H5N1, and 7.3% were co-infections with 2 of the 3 subtypes. The 32 hemagglutinin (HA) sequences of the H5N1 viruses formed a well-defined lineage within clade 2.2.1.2. The 10 HA sequences of the H5N8 viruses belonged to a subclade within 2.3.4.4. The 11 HA of H9N2 isolates showed high sequence homology with other Egyptian G1-like H9N2 viruses. The prevalence of H5N8 viruses in ducks (2.4%) was higher than in chickens (0.94%). Genetic reassortment was detected in H9N2 viruses. Antigenic analysis showed that H9N2 viruses are homogenous, antigenic drift was detected among H5N1 viruses. AI H5N8 showed higher replication rate followed by H9N2 and H5N1, respectively. H5N8 was more common in Southern Egypt, H9N2 in the Nile Delta, and H5N1 in both areas. Ducks and chickens played a significant role in transmission of H5N1 viruses. The endemicity and co-circulation of H5N1, H5N8, and H9N2 AIV coupled with the lack of a clear control strategy continues to provide avenues for further virus evolution in Egypt.

Updated unified phylogenetic classification system and revised nomenclature for Newcastle disease virus.

Several Avian paramyxoviruses 1 (synonymous with Newcastle disease virus or NDV, used hereafter) classification systems have been proposed for strain identification and differentiation. These systems pioneered classification efforts; however, they were based on different approaches and lacked objective criteria for the differentiation of isolates. These differences have created discrepancies among systems, rendering discussions and comparisons across studies difficult. Although a system that used objective classification criteria was proposed by Diel and co-workers in 2012, the ample worldwide circulation and constant evolution of NDV, and utilization of only some of the criteria, led to identical naming and/or incorrect assigning of new sub/genotypes. To address these issues, an international consortium of experts was convened to undertake in-depth analyses of NDV genetic diversity. This consortium generated curated, up-to-date, complete fusion gene class I and class II datasets of all known NDV for public use, performed comprehensive phylogenetic neighbor-Joining, maximum-likelihood, Bayesian and nucleotide distance analyses, and compared these inference methods. An updated NDV classification and nomenclature system that incorporates phylogenetic topology, genetic distances, branch support, and epidemiological independence was developed. This new consensus system maintains two NDV classes and existing genotypes, identifies three new class II genotypes, and reduces the number of sub-genotypes. In order to track the ancestry of viruses, a dichotomous naming system for designating sub-genotypes was introduced. In addition, a pilot dataset and sub-trees rooting guidelines for rapid preliminary genotype identification of new isolates are provided. Guidelines for sequence dataset curation and phylogenetic inference, and a detailed comparison between the updated and previous systems are included. To increase the speed of phylogenetic inference and ensure consistency between laboratories, detailed guidelines for the use of a supercomputer are also provided. The proposed unified classification system will facilitate future studies of NDV evolution and epidemiology, and comparison of results obtained across the world.

Global phylodynamic analysis of avian paramyxovirus-1 provides evidence of inter-host transmission and intercontinental spatial diffusion.

BACKGROUND: Avian avulavirus (commonly known as avian paramyxovirus-1 or APMV-1) can cause disease of varying severity in both domestic and wild birds. Understanding how viruses move among hosts and geography would be useful for informing prevention and control efforts. A Bayesian statistical framework was employed to estimate the evolutionary history of 1602 complete fusion gene APMV-1 sequences collected from 1970 to 2016 in order to infer viral transmission between avian host orders and diffusion among geographic regions. Ancestral states were estimated with a non-reversible continuous-time Markov chain model, allowing transition rates between discrete states to be calculated. The evolutionary analyses were stratified by APMV-1 classes I (n = 198) and II (n = 1404), and only those sequences collected between 2006 and 2016 were allowed to contribute host and location information to the viral migration networks. RESULTS: While the current data was unable to assess impact of host domestication status on APMV-1 diffusion, these analyses supported the sharing of APMV-1 among divergent host taxa. The highest supported transition rate for both classes existed from domestic chickens to Anseriformes (class I:6.18 transitions/year, 95% highest posterior density (HPD) 0.31-20.02, Bayes factor (BF) = 367.2; class II:2.88 transitions/year, 95%HPD 1.9-4.06, BF = 34,582.9). Further, among class II viruses, domestic chickens also acted as a source for Columbiformes (BF = 34,582.9), other Galliformes (BF = 34,582.9), and Psittaciformes (BF = 34,582.9). Columbiformes was also a highly supported source to Anseriformes (BF = 322.0) and domestic chickens (BF = 402.6). Additionally, our results provide support for the diffusion of viruses among continents and regions, but no interhemispheric viral exchange between 2006 and 2016. Among class II viruses, the highest transition rates were estimated from South Asia to the Middle East (1.21 transitions/year; 95%HPD 0.36-2.45; BF = 67,107.8), from Europe to East Asia (1.17 transitions/year; 95%HPD 0.12-2.61; BF = 436.2) and from Europe to Africa (1.06 transitions/year, 95%HPD 0.07-2.51; BF = 169.3). CONCLUSIONS: While migration appears to occur infrequently, geographic movement may be important in determining viral diversification and population structure. In contrast, inter-order transmission of APMV-1 may occur readily, but most events are transient with few lineages persisting in novel hosts.

Factors associated with self-reported anal cancer screening history in men who have sex with men.

Background Men who have sex with men (MSM) are at greater risk of developing anal cancer caused by human papillomavirus (HPV) than the rest of the general population. Currently, there are no formal national guidelines in the US advising men how and when to get anal cancer screening. We sought to assess differences in demographics, familiarity and anxiety about anal cancer among men who report having had anal cancer screening (i.e. anal cytology and/or a digital anorectal examination (DARE)). METHODS: MSM were recruited to participate in a study to assess the feasibility of teaching self and partner anal examinations as a means of screening for anal cancer. Data for this secondary analysis were obtained using a written pre-test and a computer-assisted self-interview. Factors associated with screening were assessed with multivariable logistic regression to allow calculation of adjusted odds ratios (aORs). RESULTS: Of the 197 participants with data, 145 (73.6%) reported having had anal cancer screening (either anal cytology, DARE or both) during their lifetime. Men who were younger, Black and HIV-negative were associated with decreased odds of reporting any type of anal cancer screening. For example, compared with White men, Black men were 80% less likely to report screening (aOR 0.2; 95% confidence interval (CI) 0.1-0.5). Self-perception of anal cancer knowledge was not associated with screening in multivariable analysis (aOR 1.6; 95% CI 0.6-3.9). CONCLUSIONS: Age, race and HIV status were independently associated with a history of anal cancer screening.

A phase II clinical study to assess the feasibility of self and partner anal examinations to detect anal canal abnormalities including anal cancer.

OBJECTIVE: Anal cancer is a common cancer among men who have sex with men (MSM); however, there is no standard screening protocol for anal cancer. We conducted a phase II clinical trial to assess the feasibility of teaching MSM to recognise palpable masses in the anal canal which is a common sign of anal cancer in men. METHODS: A clinician skilled in performing digital anorectal examinations (DARE) used a pelvic manikin to train 200 MSM, aged 27-78 years, how to do a self-anal examination (SAE) for singles or a partner anal examination (PAE) for couples. The clinician then performed a DARE without immediately disclosing results, after which the man or couple performed an SAE or PAE, respectively. Percentage agreement with the clinician DARE in addition to sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the SAE, PAE and overall. RESULTS: Men had a median age of 52 years, 42.5% were African American and 60.5% were HIV positive. DARE detected abnormalities in 12 men while the men's SAE/PAEs detected 9 of these. A total of 93.0% of men classified the health of their anal canal correctly (95% CI 89.5 to 96.5). Overall percentage agreement, sensitivity and specificity were 93.0%, 75.0% and 94.2%, respectively, while PPV and NPV were 45.0% and 98.3%, respectively. The six men who detected the abnormality had nodules/masses ≥3 mm in size. More than half of men (60.5%) reported never checking their anus for an abnormality; however, after performing an SAE/PAE, 93.0% said they would repeat it in the future. CONCLUSION: These results suggest that tumours of ≥3 mm may be detectable by self or partner palpation among MSM and encourage further investigation given literature suggesting a high cure rate for anal cancer tumours ≤10 mm.

A qualitative investigation among men who have sex with men on the acceptability of performing a self- or partner anal exam to screen for anal cancer.

PURPOSE: Persistent infection with oncogenic human papillomavirus (HPV) is the primary cause of anal cancer, a disease that disproportionately affects men who have sex with men (MSM); however, there is no uniform screening protocol to detect anal cancer. This qualitative study explores whether a self-anal exam (SAE) or partner anal exam (PAE), that includes self-palpation or palpation of a partner's anal canal, is an acceptable and self-efficacious screening test, which will cue appropriate follow-up care in MSM. METHODS: Twenty-four MSM living in Houston took part in four focus group sessions eliciting their responses to a study teaching them to perform an SAE or PAE (SAE/PAE). Participants were asked about the acceptability and feasibility of executing an SAE/PAE routinely. Thematic analysis of session transcripts was used to identify common patterns in participant responses. RESULTS: Overall, participants expressed self-efficacy for performing an SAE/PAE and voiced a preference for being taught the procedure by a clinician. Participants agreed that they would consult with a clinician if they ever discovered an abnormality while performing an SAE/PAE. A lack of knowledge about anal cancer among MSM may present a barrier to adopting SAE/PAE. In discussing their experience of the exams, some participants suggested that it could become a routine practice for them. CONCLUSIONS: Our findings suggest that SAE and PAE, as a screen for anal cancer, are acceptable and feasible to MSM. Future research should explore attitudes and beliefs of MSM, with the aim of improving anal cancer education and understanding of pathologic findings.

Assessment of contemporary genetic diversity and inter-taxa/inter-region exchange of avian paramyxovirus serotype 1 in wild birds sampled in North America.

BACKGROUND: Avian paramyxovirus serotype 1 (APMV-1) viruses are globally distributed, infect wild, peridomestic, and domestic birds, and sometimes lead to outbreaks of disease. Thus, the maintenance, evolution, and spread of APMV-1 viruses are relevant to avian health. METHODS: In this study we sequenced the fusion gene from 58 APMV-1 isolates recovered from thirteen species of wild birds sampled throughout the USA during 2007-2014. We analyzed sequence information with previously reported data in order to assess contemporary genetic diversity and inter-taxa/inter-region exchange of APMV-1 in wild birds sampled in North America. RESULTS: Our results suggest that wild birds maintain previously undescribed genetic diversity of APMV-1; however, such diversity is unlikely to be pathogenic to domestic poultry. Phylogenetic analyses revealed that APMV-1 diversity detected in wild birds of North America has been found in birds belonging to numerous taxonomic host orders and within hosts inhabiting multiple geographic regions suggesting some level of viral exchange. However, our results also provide statistical support for associations between phylogenetic tree topology and host taxonomic order/region of sample origin which supports restricted exchange among taxa and geographical regions of North America for some APMV-1 sub-genotypes. CONCLUSIONS: We identify previously unrecognized genetic diversity of APMV-1 in wild birds in North America which is likely a function of continued viral evolution in reservoir hosts. We did not, however, find support for the emergence or maintenance of APMV-1 strains predicted to be pathogenic to poultry in wild birds of North America outside of the order Suliformes (i.e., cormorants). Furthermore, genetic evidence suggests that ecological drivers or other mechanisms may restrict viral exchange among taxa and regions of North America. Additional and more systematic sampling for APMV-1 in North America would likely provide further inference on viral dynamics for this infectious agent in wild bird populations.