Human Epidemics Research Articles

Hemophilia: The Past, the Present, and the Future.

Hemophilia: The Past, the Present, and the Future.

Emergent Arboviruses: A Review About Mayaro virus and Oropouche orthobunyavirus

Arthropod-borne viruses have a significant impact on public health worldwide, and their (re) emergence put aside the importance of other circulating arboviruses. Therefore, this scoping review aims to identify and characterize the literature produced in recent years, focusing on aspects of two arboviruses: Mayaro virus and Oropouche orthobunyavirus. The Mayaro and Oropouche viruses were isolated for the first time in Trinidad and Tobago in 1954 and 1955, respectively, and have more recently caused numerous outbreaks. In addition, they have been incriminated as candidate diseases for human epidemics. These viruses have been drawing the attention of public health authorities worldwide following recent outbreaks. To determine the global epidemiological profile of these viruses, we used the Dimensions Database, which contains more than 100 million publications. In general, we identified 327 studies published from 1957 to 2020 for Mayaro virus, and 152 studies published from 1961 to 2020 for Oropouche orthobunyavirus. Interestingly, we observed that Mayaro and Oropouche had a significant increase in the number of publications in recent years. Thus, this comprehensive review will be helpful to guide future research based on the identified knowledge gaps.

Managing Science Communication in a Post-Truth Era

SPEAKER: Jessica Malaty Rivera Science Communication Lead for the COVID Tracking Project REPORTER: El-shama Q.A Nwoko African Journal of Laboratory Medicine Plenary speaker Jessica Malaty Rivera is an Infectious Disease Epidemiologist and Science Communicator with 15 years of experience in disease surveillance research, public policy, and vaccine advocacy. She began her presentation by giving a background of her education and experience, then went on to share some best practices she has picked up through the years, which were implemented in the COVID Tracking Project. She concluded by sharing the aim, language, and science of science communication. Background Malaty Rivera received her Master of Science degree in Emerging and Infectious Diseases from Georgetown University 10 years ago. After that time, she worked at the now defunded Division of Integrated Biodefence at Georgetown. The Division focused on biosurveillance, serving as an “infectious disease Weather Channel” that identified indicators and warnings of emerging animal and human epidemics and pandemics. The Division translated information from over 50 different languages into reports and algorithms for predicting the severity of impending outbreaks. Using this approach, the Division detected the 2009 H1N1 Pandemic. This experience, Malaty Rivera says, prepared her for her role as a science communicator. Sadly, she noted that the Division could not detect the COVID-19 pandemic because it was devalued and ultimately defunded. She reemphasized the role of biosurveillance in pandemic preparedness and stated its current lacking hugely contributed to the COVID-19 pandemic unpreparedness as there would have been some warning indicators in […]

Evolution of human respiratory virus epidemics.

Background: Pathogens are often assumed to evolve towards reduced virulence, but counterexamples abound. Faced with a new pathogen, such as SARS-CoV-2, it is crucial to be able to forecast the case fatality rate (CFR) and the overall disease burden. Considerable effort has been invested towards developing a mathematical framework for predicting virulence evolution. Although many approaches accurately recapitulate complex outcomes, most rely on an assumed trade-off between CFR and infection rate. It is often impractical to empirically validate this constraint for human pathogens. Methods: A compartment model with parameters tuning the degree to which symptomatic individuals are isolated and the duration of immunity is constructed and evaluated at both short timescales and at equilibrium. Results: We reveal kinetic constraints whereby variation of multiple parameters in concert leads to decreased CFR and increased pathogen fitness, whereas independent variation of the parameters decreases pathogen fitness. Smallpox, SARS-CoV-2, and influenza are analyzed as diverse representatives of human respiratory viruses. We show that highly virulent viruses, such as smallpox, are often constrained by the host behavior, whereas moderately virulent viruses, such as SARS-CoV-2, appear to be typically constrained by the relationship between the duration of immunity and CFR. Conclusions: Evolution of human respiratory epidemics appears to be often kinetically constrained and a reduction in CFR should not be assumed. These results agree with previous work demonstrating an increase in virulence for smallpox and further predict that SARS-CoV-2 is likely to continue presenting a substantial disease burden. Herd immunity against SARS-CoV-2 and viruses with similar life history traits might be unachievable without vaccination. However, partial isolation of symptomatic individuals can have a major effect on the epidemic dynamics not only by reducing the number of fatalities in the short term but also by changing the evolutionary trajectory of moderate CFR viruses towards reduced CFR.

Evolution of human respiratory virus epidemics

Background: Pathogens are often assumed to evolve towards reduced virulence, but counterexamples abound. Faced with a new pathogen, such as SARS-CoV-2, it is crucial to be able to forecast the case fatality rate (CFR) and the overall disease burden. Considerable effort has been invested towards developing a mathematical framework for predicting virulence evolution. Although many approaches accurately recapitulate complex outcomes, most rely on an assumed trade-off between CFR and infection rate. It is often impractical to empirically validate this constraint for human pathogens.Methods: A compartment model with parameters tuning the degree to which symptomatic individuals are isolated and the duration of immunity is constructed and evaluated at both short timescales and at equilibrium.Results: We reveal kinetic constraints whereby variation of multiple parameters in concert leads to decreased CFR and increased pathogen fitness, whereas independent variation of the parameters decreases pathogen fitness. Smallpox, SARS-CoV-2, and influenza are analyzed as diverse representatives of human respiratory viruses. We show that highly virulent viruses, such as smallpox, are often constrained by the host behavior, whereas moderately virulent viruses, such as SARS-CoV-2, appear to be typically constrained by the relationship between the duration of immunity and CFR.Conclusions: Evolution of human respiratory epidemics appears to be often kinetically constrained and a reduction in CFR should not be assumed. These results agree with previous work demonstrating an increase in virulence for smallpox and further predict that SARS-CoV-2 is likely to continue presenting a substantial disease burden. Herd immunity against SARS-CoV-2 and viruses with similar life history traits might be unachievable without vaccination. However, partial isolation of symptomatic individuals can have a major effect on the epidemic dynamics not only by reducing the number of fatalities in the short term but also by changing the evolutionary trajectory of moderate CFR viruses towards reduced CFR.

The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysis

Dog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the last nation-wide dog vaccination campaign occurred in 2018. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios. We modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005 to 2025, with varying assumptions about when dog vaccinations resume. We compared model outputs to surveillance data on human rabies deaths from 2005 to 2020 and animal rabies cases from 2018 to 2020. Model predictions and surveillance data both suggest a 5- to 8-fold increase in animal rabies cases occurred in Haiti’s capital city between Fall 2019 and Fall 2020. Restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6541 human rabies exposures over a five-year period. It may also decrease program costs due to reduced need for human post-exposure prophylaxis. These results show that interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.

Evolution of human respiratory virus epidemics.

Background: It is often assumed that pathogens evolve towards reduced virulence, but counterexamples abound. Faced with a new pathogen, such as SARS-CoV-2, it is highly desirable to be able to forecast the case fatality rate (CFR) and overall disease burden into the future. Considerable effort has been invested towards the development of a mathematical framework for predicting virulence evolution. Although many approaches accurately recapitulate complex outcomes, most rely on an assumed trade-off between CFR and infection rate. It is often impractical to empirically validate this constraint for human pathogens. Methods: A compartment model with parameters tuning the degree to which symptomatic individuals are isolated and the duration of immunity is constructed and evaluated at both short timescales and at equilibrium (when it exists). Results: We reveal kinetic constraints where the variation of multiple parameters in concert leads to decreased CFR and increased pathogen fitness, whereas independent variation of the parameters decreases pathogen fitness. Smallpox, SARS-CoV-2, and influenza are analyzed as diverse representatives of human respiratory viruses. We show that highly virulent viruses, such as smallpox, are likely often constrained by host behavior, whereas moderately virulent viruses, such as SARS-CoV-2, appear to be typically constrained by the relationship between the duration of immunity and CFR. Conclusions: Evolution of human respiratory epidemics appears to be often kinetically constrained and a reduction in CFR should not be assumed. Our findings imply that, without continued public health intervention, SARS-CoV-2 is likely to continue presenting a substantial disease burden. The existence of a parameter regime admitting endemic equilibrium suggests that herd immunity is unachievable. However, we demonstrate that even partial isolation of symptomatic individuals can have a major effect not only by reducing the number of fatalities in the short term but also by potentially changing the evolutionary trajectory of the virus towards reduced CFR.

Initial growth rates of malware epidemics fail to predict their reach

Empirical studies show that epidemiological models based on an epidemic’s initial spread rate often fail to predict the true scale of that epidemic. Most epidemics with a rapid early rise die out before affecting a significant fraction of the population, whereas the early pace of some pandemics is rather modest. Recent models suggest that this could be due to the heterogeneity of the target population’s susceptibility. We study a computer malware ecosystem exhibiting spread mechanisms resembling those of biological systems while offering details unavailable for human epidemics. Rather than comparing models, we directly estimate reach from a new and vastly more complete data from a parallel domain, that offers superior details and insight as concerns biological outbreaks. We find a highly heterogeneous distribution of computer susceptibilities, with nearly all outbreaks initially over-affecting the tail of the distribution, then collapsing quickly once this tail is depleted. This mechanism restricts the correlation between an epidemic’s initial growth rate and its total reach, thus preventing the majority of epidemics, including initially fast-growing outbreaks, from reaching a macroscopic fraction of the population. The few pervasive malwares distinguish themselves early on via the following key trait: they avoid infecting the tail, while preferentially targeting computers unaffected by typical malware.

Prevalence, Serovars, and Factors Associated with Salmonella Contamination of Chicken Carcasses Sold in Outlets of the Informal Market in Gauteng Province, South Africa

Salmonella has been linked to many foodborne illnesses and epidemics in both humans and animals. This cross-sectional study determined the prevalence, serovars, and factors associated with Salmonella contamination of chickens slaughtered in informal market outlets in Gauteng Province, South Africa. A total of 151 chicken carcasses were randomly collected from 47 outlets. Standard bacteriological and molecular methods were used to isolate, identify, and determine the serovar of Salmonella isolates. The prevalence of Salmonella in carcass swabs, cloacal swabs, and carcass drips was 29.1% (44 of 151), 27.2% (41 of 151), and 43.7% (66 of 151), respectively, and the differences were statistically significant (P = 0.004). Only 5 (township locations of outlet, throughput, carcass evisceration, location of carcass for sale, and outlet sanitation) of 10 factors investigated for the contamination of carcasses by Salmonella were statistically significantly (P < 0.05) associated with the isolation of Salmonella. Of the 268 isolates of Salmonella, 157 (58.6%) were typeable using a limited molecular PCR technique, and nine serovars were identified. The predominant Salmonella enterica serovars were Bovismorbificans (31.0%), Enteritidis (7.5%), and Hadar (6.7%). The five important factors found to be significantly associated with the isolation of Salmonella at these outlets offer opportunities for the reduction of Salmonella contamination. There is a need for further investigation of the probable causes of the predominant isolation of Salmonella serovar Bovismorbificans in chickens and its potential implications for human infections in South Africa. It is concluded that chickens purchased from the informal market in Gauteng Province can be a source for salmonellosis in humans if improperly cooked before consumption.

Development of Lentiviral Vectors Pseudotyped With Influenza B Hemagglutinins: Application in Vaccine Immunogenicity, mAb Potency, and Sero-Surveillance Studies.

Influenza B viruses (IBV) cause respiratory disease epidemics in humans and are therefore components of seasonal influenza vaccines. Serological methods are employed to evaluate vaccine immunogenicity prior to licensure. However, classical methods to assess influenza vaccine immunogenicity such as the hemagglutination inhibition assay (HI) and the serial radial hemolysis assay (SRH), have been proven to have many limitations. As such, there is a need to develop innovative methods that can improve on these traditional assays and provide advantages such as ease of production and access, safety, reproducibility, and specificity. It has been previously demonstrated that the use of replication-defective viruses, such as lentiviral vectors pseudotyped with influenza A hemagglutinins in microneutralization assays (pMN) is a safe and sensitive alternative to study antibody responses elicited by natural influenza infection or vaccination. Consequently, we have produced Influenza B hemagglutinin-pseudotypes (IBV PV) using plasmid-directed transfection. To activate influenza B hemagglutinin, we have explored the use of proteases in increasing PV titers via their co-transfection during pseudotype virus production. When tested for their ability to transduce target cells, the influenza B pseudotypes produced exhibit tropism for different cell lines. The pseudotypes were evaluated as alternatives to live virus in microneutralization assays using reference sera standards, mouse and human sera collected during vaccine immunogenicity studies, surveillance sera from seals, and monoclonal antibodies (mAbs) against IBV. The influenza B pseudotype pMN was found to effectively detect neutralizing and cross-reactive responses in all assays and shows promise as an effective and versatile tool in influenza research.

Viewing Emerging Human Infectious Epidemics through the Lens of Invasion Biology

Abstract Invasion biology examines species originated elsewhere and moved with the help of humans, and those species’ impacts on biodiversity, ecosystem services, and human well-being. In a globalized world, the emergence and spread of many human infectious pathogens are quintessential biological invasion events. Some macroscopic invasive species themselves contribute to the emergence and transmission of human infectious agents. We review conceptual parallels and differences between human epidemics and biological invasions by animals and plants. Fundamental concepts in invasion biology regarding the interplay of propagule pressure, species traits, biotic interactions, eco-evolutionary experience, and ecosystem disturbances can help to explain transitions between stages of epidemic spread. As a result, many forecasting and management tools used to address epidemics could be applied to biological invasions and vice versa. Therefore, we advocate for increasing cross-fertilization between the two disciplines to improve prediction, prevention, treatment, and mitigation of invasive species and infectious disease outbreaks, including pandemics.

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

SummaryCoronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

Dynamic Dissection of the Endocytosis of Porcine Epidemic Diarrhea Coronavirus Cooperatively Mediated by Clathrin and Caveolae as Visualized by Single-Virus Tracking.

Coronaviruses (CoVs) have caused severe diseases in humans and animals. Endocytic pathways, such as clathrin-mediated endocytosis (CME) and caveolae-mediated endocytosis (CavME), play an important role for CoVs to penetrate the cell membrane barrier. In this study, a novel CoV entry manner is unraveled in which clathrin and caveolae can cooperatively mediate endocytosis of porcine epidemic diarrhea coronavirus (PEDV). Using multicolor live-cell imaging, the dynamics of the fluorescently labeled clathrin structures, caveolae structures, and PEDV were dissected. During CavME of PEDV, we found that clathrin structures can fuse with caveolae near the cell plasma membrane, and the average time of PEDV penetrating the cell membrane was within ∼3 min, exhibiting a rapid course of PEDV entry. Moreover, based on the dynamic recruitment of clathrin and caveolae structures and viral motility, the direct evidence also shows that about 20% of PEDVs can undergo an abortive entry via CME and CavME. Additionally, the dynamic trafficking of PEDV from clathrin and caveolae structures to early endosomes, and from early endosomes to late endosomes, and viral fusion were directly dissected, and PEDV fusion mainly occurred in late endosomes within ∼6.8 min after the transport of PEDV to late endosomes. Collectively, this work systematically unravels the early steps of PEDV infection, which expands our understanding of the mechanism of CoV infection.IMPORTANCE Emerging and re-emerging coronaviruses cause serious human and animal epidemics worldwide. For many enveloped viruses, including coronavirus, it is evident that breaking the plasma membrane barrier is a pivotal and complex process, which contains multiple dynamic steps. Although great efforts have been made to understand the mechanisms of coronavirus endocytic pathways, the direct real-time imaging of individual porcine epidemic diarrhea coronavirus (PEDV) internalization has not been achieved yet. In this study, we not only dissected the kinetics of PEDV entry via clathrin-mediated endocytosis and caveolae-mediated endocytosis and the kinetics of endosome trafficking and viral fusion but also found a novel productive coronavirus entry manner in which clathrin and caveolae can cooperatively mediate endocytosis of PEDV. Moreover, we uncovered the existence of PEDV abortive endocytosis. In summary, the productive PEDV entry via the cooperation between clathrin and caveolae structures and the abortive endocytosis of PEDV provide new insights into coronavirus penetrating the plasma membrane barrier.

User - provider perspectives to overcome the challenges of TB/HIV service integration at Mulago National Referral Hospital _ Kampala.

Tuberculosis and Human Immunodeficiency Virus epidemics in sub-Saharan Africa have been closely related and persistent, proving a considerable burden for healthcare provision. This has complicated utilization of services, with noted opinions on the integration of these services from both users and providers of the services. To establish the users and the provider's perspectives in overcoming the challenges of TB/HIV services integration at Mulago National Referral Hospital. Descriptive cross-sectional design, with predominantly qualitative methods was used. Qualitative aspect adopted phenomenological design. Participants were randomly selected for FGDs and Key informants. An observation checklist collected quantitative data from the patients to measure level of services integration. Level of service integration of TB/HIV services was at 68% (below the acceptable 100% level). Opinions from the users pointed to; increasing number of work-days for TB/HIV service provision, strengthening sensitisation and health education and integrating other services like reproductive health services, among others. Health care providers opinions pointed to increasing trainings for health workers, increasing staffing and need for more support from Ministry of Health. Opinions from both users and providers were similar. These ranged from increasing awareness to the users and healthcare providers about the integration of services.

Roles of host small RNAs in the evolution and host tropism of coronaviruses.

Human coronaviruses (CoVs) can cause respiratory infection epidemics that sometimes expand into globally relevant pandemics. All human CoVs have sister strains isolated from animal hosts and seem to have an animal origin, yet the process of host jumping is largely unknown. RNA interference (RNAi) is an ancient mechanism in many eukaryotes to defend against viral infections through the hybridization of host endogenous small RNAs (miRNAs) with target sites in invading RNAs. Here, we developed a method to identify potential RNAi-sensitive sites in the viral genome and discovered that human-adapted coronavirus strains had deleted some of their sites targeted by miRNAs in human lungs when compared to their close zoonic relatives. We further confirmed using a phylogenetic analysis that the loss of RNAi-sensitive target sites could be a major driver of the host-jumping process, and adaptive mutations that lead to the loss-of-target might be as simple as point mutation. Up-to-date genomic data of severe acute respiratory syndrome coronavirus 2 and Middle-East respiratory syndromes-CoV strains demonstrate that the stress from host miRNA milieus sustained even after their epidemics in humans. Thus, this study illustrates a new mechanism about coronavirus to explain its host-jumping process and provides a novel avenue for pathogenesis research, epidemiological modeling, and development of drugs and vaccines against coronavirus, taking into consideration these findings.

While We Endure This Pandemic, What New Respiratory Virus Threats Are We Missing?

In this paper, we review recent human respiratory virus epidemics, their zoonotic nature, and our current inability to identify future prepandemic threats. We propose a cost-efficient, One Health surveillance strategy that will be more efficient and more sustainable than previous efforts.

Sialic Acid Receptors: The Key to Solving the Enigma of Zoonotic Virus Spillover.

Emerging viral diseases are a major threat to global health, and nearly two-thirds of emerging human infectious diseases are zoonotic. Most of the human epidemics and pandemics were caused by the spillover of viruses from wild mammals. Viruses that infect humans and a wide range of animals have historically caused devastating epidemics and pandemics. An in-depth understanding of the mechanisms of viral emergence and zoonotic spillover is still lacking. Receptors are major determinants of host susceptibility to viruses. Animal species sharing host cell receptors that support the binding of multiple viruses can play a key role in virus spillover and the emergence of novel viruses and their variants. Sialic acids (SAs), which are linked to glycoproteins and ganglioside serve as receptors for several human and animal viruses. In particular, influenza and coronaviruses, which represent two of the most important zoonotic threats, use SAs as cellular entry receptors. This is a comprehensive review of our current knowledge of SA receptor distribution among animal species and the range of viruses that use SAs as receptors. SA receptor tropism and the predicted natural susceptibility to viruses can inform targeted surveillance of domestic and wild animals to prevent the future emergence of zoonotic viruses.

Chemokine Regulation During Epidemic Coronavirus Infection.

SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus-2) is the third coronavirus to emerge as a cause of severe and frequently fatal pneumonia epidemics in humans, joining SARS-CoV and MERS-CoV (Middle East Respiratory Syndrome-coronavirus). As with many infectious diseases, the immune response to coronavirus infection may act as a double-edged sword: necessary for promoting antiviral host defense, but, if not appropriately regulated, also able to incite life-threatening immunopathology. Key immunoregulatory mediators include the chemokines, a large family of leukocyte chemoattractants that coordinate leukocyte infiltration, positioning and activation in infected tissue by acting at specific G protein-coupled receptors. Here, we compare the involvement of chemokines and chemokine receptors during infection with the three epidemic coronaviruses and discuss their potential value as biomarkers and targets for therapeutic development.

Silicon nitride: a potent solid-state bioceramic inactivator of ssRNA viruses

Surface inactivation of human microbial pathogens has a long history. The Smith Papyrus (2600 ~ 2200 B.C.) described the use of copper surfaces to sterilize chest wounds and drinking water. Brass and bronze on doorknobs can discourage microbial spread in hospitals, and metal-base surface coatings are used in hygiene-sensitive environments, both as inactivators and modulators of cellular immunity. A limitation of these approaches is that the reactive oxygen radicals (ROS) generated at metal surfaces also damage human cells by oxidizing their proteins and lipids. Silicon nitride (Si3N4) is a non-oxide ceramic compound with known surface bacterial resistance. We show here that off-stoichiometric reactions at Si3N4 surfaces are also capable of inactivating different types of single-stranded RNA (ssRNA) viruses independent of whether their structure presents an envelop or not. The antiviral property of Si3N4 derives from a hydrolysis reaction at its surface and the subsequent formation of reactive nitrogen species (RNS) in doses that could be metabolized by mammalian cells but are lethal to pathogens. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of viral RNA and in situ Raman spectroscopy suggested that the products of Si3N4 hydrolysis directly react with viral proteins and RNA. Si3N4 may have a role in controlling human epidemics related to ssRNA mutant viruses.

Climate change affected the spatio-temporal occurrence of disasters in China over the past five centuries

Climate change may contribute to the spatio-temporal occurrence of disasters. Long-term studies of either homogeneous or heterogeneous responses of historical disasters to climate change are, however, limited by the quality and quantity of the available proxy data. Here we reconstruct spatio-temporal patterns of five types of disasters in China during the period AD 1368–1911. Our analyses of these time series reveal that warmer temperatures decreased the occurrence of disasters in the monsoon-affected parts of central-east China, but it increased the frequency and intensity of disasters along the boundary of arid and humid conditions in parts of southwest and northeast China, probably driven by the interplay among monsoon, westerlies, polar vortex and variation of temperature. Moreover, we show that drought and flood events had cascading effects on the occurrences of locust outbreaks, famine and human epidemics. Our findings suggest that climate can contribute to the spatio-temporal occurrence of disasters, and therefore may contribute to an improvement of China's regional to national risk management of future climate and environmental change.