Arbovirus and its potential to lead the next global pandemic from sub-Saharan Africa: What lessons have we learned from COVID-19?

Risk and predisposing factors for viral zoonoses abound in the sub-Saharan Africa (SSA) region with significant public health implications. For several decades, there have been several reports on the emergence and re-emergence of arbovirus infections. The lifetime burden of arboviral diseases in developing countries is still poorly understood. Studies indicate significant healthcare disruptions and economic losses attributed to the viruses in resource-poor communities marked by impairment in the performance of daily activities. Arboviruses have reportedly evolved survival strategies to aid their proliferation in favorable niches, further magnifying their public health relevance. However, there is poor knowledge about the viruses in the region. Thus, this review presents a survey of zoonotic arboviruses in SSA, the burden associated with their diseases, management of diseases as well as their prevention and control, mobility and determinants of infections, their vectors, and co-infection with various microorganisms. Lessons learned from the ongoing coronavirus disease 2019 (COVID-19) pandemic coupled with routine surveillance of zoonotic hosts for these viruses will improve our understanding of their evolution, their potential to cause a pandemic, control and prevention measures, and vaccine development.Copyright © GERMS 2022.

West Nile virus infections in Hungary: Epidemiological update and phylogenetic analysis of the Hungarian virus strains between 2015 and 2022.

Following the introduction of the West Nile virus (WNV) into Hungary in 2004, it has shortly become one of the most important human arbovirus infections, with a gradually increasing number of cases. The study aimed to summarize the current epidemiological situation in Hungary and sequence the WNV PCR-positive clinical specimens and virus isolates by next-generation whole genome sequencing (NGS) to obtain a detailed phylogenetic analysis of the circulating virus strains. Whole blood and urine samples from confirmed WNV-infected patients and WNV isolates were investigated by reverse transcription PCR assays. Genome sequencing was carried out by Sanger-method, followed by NGS on the Illumina MiSeq platform. Altogether 499 human infections were diagnosed between 2004 and 2022. A particularly remarkable increase in human WNV infections was observed in 2018, while the number of reported cases significantly decreased during the COVID-19 pandemic. Between 2015 and 2022, 15 WNV isolates, and 10 PCR-positive clinical specimens were investigated by NGS. Phylogenetic analysis revealed that the major European WNV lineage 2 clades, namely the Eastern European (or Russian) and the Central European (or Hungarian) clades, are presented in Hungary. Strains of the Balkan and other European clusters within the Central European clade are co-circulating in the country, following a characteristic geographical distribution. In Hungary, the presence and co-circulation of multiple lineage 2 WNV strains could be identified in the last few years. Therefore, in light of the 2018 WNV outbreak, sequence-based typing of the currently circulating strains could highly support outbreak investigations.

[130th anniversary of virology].

130 years ago, in 1892, our great compatriot Dmitry Iosifovich Ivanovsky (18641920) discovered a new type of pathogen viruses. Viruses have existed since the birth of life on Earth and for more than three billion years, as the biosphere evolved, they are included in interpopulation interactions with representatives of all kingdoms of life: archaea, bacteria, protozoa, algae, fungi, plants, invertebrates, and vertebrates, including the Homo sapiens (Hominidae, Homininae). Discovery of D.I. Ivanovsky laid the foundation for a new science virology. The rapid development of virology in the 20th century was associated with the fight against emerging and reemerging infections, epidemics (epizootics) and pandemics (panzootics) of which posed a threat to national and global biosecurity (tick-borne and other encephalitis, hemorrhagic fevers, influenza, smallpox, poliomyelitis, HIV, parenteral hepatitis, coronaviral and other infections). Fundamental research on viruses created the basis for the development of effective methods of diagnostics, vaccine prophylaxis, and antiviral drugs. Russian virologists continue to occupy leading positions in some priority areas of modern virology in vaccinology, environmental studies oz zoonotic viruses, studies of viral evolution in various ecosystems, and several other areas. A meaningful combination of theoretical approaches to studying the evolution of viruses with innovative methods for studying their molecular genetic properties and the creation of new generations of vaccines and antiviral drugs on this basis will significantly reduce the consequences of future pandemics or panzootics. The review presents the main stages in the formation and development of virology as a science in Russia with an emphasis on the most significant achievements of soviet and Russian virologists in the fight against viral infectious diseases.

Widespread Exposure to Mosquitoborne California Serogroup Viruses in Caribou, Arctic Fox, Red Fox, and Polar Bears, Canada.

Northern Canada is warming at 3 times the global rate. Thus, changing diversity and distribution of vectors and pathogens is an increasing health concern. California serogroup (CSG) viruses are mosquitoborne arboviruses; wildlife reservoirs in northern ecosystems have not been identified. We detected CSG virus antibodies in 63% (95% CI 58%-67%) of caribou (n = 517), 4% (95% CI 2%-7%) of Arctic foxes (n = 297), 12% (95% CI 6%-21%) of red foxes (n = 77), and 28% (95% CI 24%-33%) of polar bears (n = 377). Sex, age, and summer temperatures were positively associated with polar bear exposure; location, year, and ecotype were associated with caribou exposure. Exposure was highest in boreal caribou and increased from baseline in polar bears after warmer summers. CSG virus exposure of wildlife is linked to climate change in northern Canada and sustained surveillance could be used to measure human health risks.

Identifying Japanese Encephalitis Virus Using Metatranscriptomic Sequencing, Xinjiang, China.

The treat of infectious disease epidemics has increased the critical need for continuous broad-ranging surveillance of pathogens with outbreak potential. Using metatranscriptomic sequencing of blood samples, we identified several cases of Japanese encephalitis virus infection from Xinjiang Uyghur Autonomous Region, China. This discovery highlights the risk for known viral diseases even in nonendemic areas.

Potential impact of SARS COV-2 infection on the performance of serological assays used to diagnose arboviral diseases.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 was first described in December 2019, in China. In addition, there has also been an increase in arboviral infections in recent years. As both infections have similar symptoms, misdiagnosis may occur if both outbreaks occur at the same time. OBJECTIVE: Our objective was to assess the potential impact of SARS-CoV-2 infection on diagnostic assays used for arboviral diseases. MATERIALS AND METHODS: We conducted this study by testing samples obtained during the precovid phase (before November 2019) and during the covid period (after February 2020). Samples were further grouped as those with acute febrile illness (AFI) and those without. All samples were tested for anti SARS-CoV-2 Ab, Chikungunya and Dengue specific IgM antibodies to evaluate potential serological cross-reactions between COVID-19 and Arbovirus specific antibodies. RESULTS: One sample from the 62 cases of AFI during the pre-covid phase showed seropositivity for SARS-CoV-2 antibodies. Also, in asymptomatic individuals, arboviral seropositivity was significantly higher in the COVID period samples (22%) compared to pre-COVID samples (3%). CONCLUSION: Due to similar clinical symptoms and cross reactions in both infections, relying solely on serological testing for arboviral diagnosis may be less sensitive; other clinical and laboratory parameters may be required.

A study on the role of aedes mosquitoes in arboviruses and SARS-CoV-2 infection: A new challenge.

Chikungunya, Zika, Dengue Viruses, and now Novel Coronavirus are global health challenges that cause human diseases ranging from febrile illnesses to death. Most of these viruses are mainly vectored by Aedes mosquitoes worldwide. Molecular detection of arboviruses was made in female Aedes mosquito pools caught from all the seven districts by using a reliable molecular technique, "RT-PCR." From 216 collections of Aedes species, arboviruses were detected in 27, including only Alphavirus genus to determine mosquito abundance and evaluate the potential role of Aedes aegypti and Ae. albopictus mosquitoes in arboviruses and nvel Coronavirus transmission. 5322 mosquitoes were collected using aspirators; 35.31% (n = 2049) were identified as female Aedes using morphological keys, pooled into 216 pools, and tested for arboviruses and coronaviruses by using RT-PCR with the help of specific primers. Novel Coronavirus was not detected in this study. Only the Flavivirus genus was detected in twenty-seven pools giving an infection rate of 62.96% (n = 17) for DENV2, while DENV3 was 37.03% (n = 10). Furthermore, our results indicated no role of mosquitoes in the spread of Covid-19. Results showed a higher infection rate in urban sites than in rural ones. The detection of arboviruses indicates possible human health risk due to active role of these mosquitoes in spreading of arbovirus in the study area.

Special Issue: Microbiologists making waves around the South Pacific. (Special Issue: Microbiologists making waves around the South Pacific.)

This special issue includes 11 articles focusing on development of container laboratories in response to COVID-19;COVID-19 in Fiji;Pacific Regional Infectious Disease Association (PRIDA) - capacity-building for microbiology and infectious disease across the Pacific;meningococcal surveillance in Southeast Asia and the Pacific;tropical fever in remote tropics;movement of arboviruses between Indonesia and Western Australia;Rotavirus surveillance informs diarrhoea disease burden in the WHO Western-Pacific region;surveillance for One Health and high consequence veterinary pathogens (Brucellosis, Coxiellosis and Foot and Mouth Disease) in Southeast Asia - Lao PDR and Cambodia in focus and the importance of international partnerships;Avian influenza H5N1.

Bioprospecting for Antiviral Peptides

Mosquito-borne alphaviruses (e.g. chikungunya virus and Venezuelan equine encephalitis virus-VEEV) are of great concern due to their potential to cause severe acute human disease. The absence of available vaccines or therapeutic agents for almost all arboviruses makes development of effective treatment options a significant national security and public health issue. Here, we focus on the study of VEEV as a model arbovirus. Cationic antimicrobial peptides (CAMPs) of innate immunity represent a promising resource for the development of new antiviral therapeutics. However, there is need for a system specifically designed for purpose of discovering AMPs with antiviral activity. We aim to develop a bioprospecting-inspired process for the identification of antiviral peptides against VEEV, using an integrated workflow that combines novel antiviral peptide harvesting microparticles, advanced mass spectrometry, and data analysis tools in order to establish peptide sequences and identify those with potential antiviral properties. We will focus on alligators and snakes CAMPs, since both have been suggested as potential arbovirus reservoir species.

A molecular surveillance-guided vector control response to concurrent dengue and West Nile virus outbreaks in a COVID-19 hotspot of Florida.

Background: Simultaneous dengue virus (DENV) and West Nile virus (WNV) outbreaks in Florida, USA, in 2020 resulted in 71 dengue virus serotype 1 and 86 WNV human cases. We hypothesized that we would find a number of DENV-1 positive mosquito pools, and that the distribution of these arbovirus-positive mosquito pools would be associated with those neighborhoods for which imported DENV cases have been recently reported in 2019 and 2020. Methods: We collected and screened Aedes aegypti, Ae. albopictus, Anopheles crucians, Culex coronator, Cx. nigripalpus, and Cx. quinquefasciatus mosquitoes from Miami-Dade County (Florida) for DENV and WNV by rRT-qPCR. Spatial statistical analyses were performed to capture positive mosquito pool distribution in relation to land use, human demography, environmental variables, mosquito trap placement and reported human travel associated DENV cases to guide future mosquito control outbreak responses. Findings: A rapid screen of 7,668 mosquitoes detected four DENV serotype 2 (DENV-2), nine DENV-4 and nine WNV-positive mosquito pools, which enabled swift and targeted abatement of trap sites by mosquito control. As expected, DENV-positive pools were in urban areas; however, we found WNV-positive mosquito pools in agricultural and recreational areas with no historical reports of WNV transmission. Interpretation: These findings demonstrate the importance of proactive arbovirus surveillance in mosquito populations to prevent and control outbreaks, particularly when other illnesses (e.g., COVID-19), which present with similar symptoms, are circulating concurrently. Growing evidence for substantial infection prevalence of dengue in mosquitoes in the absence of local index cases suggests a higher level of dengue endemicity in Florida than previously thought. Funding: This research was supported in part by U.S. Centers for Disease Control and Prevention (CDC) grant 1U01CK000510-03, Southeastern Regional Center of Excellence in Vector Borne Diseases Gateway Program.

Autochthonous West Nile virus infection in Germany: Increasing numbers and a rare encephalitis case in a kidney transplant recipient.

West Nile Virus (WNV) infections are increasingly detected in birds and horses in central Europe, with the first mosquito-borne autochthonous human infection detected in Germany in 2019. Human infections are typically asymptomatic, with occasional severe neurological disease. Because of a low number of cases in central Europe, awareness regarding potential cases is low and WNV diagnostic testing is not routine. We tested cerebrospinal fluid (CSF) samples from unsolved encephalitis and meningitis cases from Berlin from 2019 to 2020, and describe a WNV-encephalitis case in a 33-year-old kidney transplant recipient. The infectious course was resolved by serology, RT-PCR and sequencing of stored samples. Phylogenetic sequence analysis revealed a close relationship of the patient's WNV strain to German sequences from 2019 and 2020. A lack of travel history and patient self-isolation during the SARS-CoV-2 pandemic suggest the infection was acquired in the patient's home or garden. Serological tests of four people sharing the living space were negative. Retrospective RT-PCR and WNV-IgM testing of 671 CSF samples from unsolved encephalitis and meningitis cases from Berlin detected no additional infections. The recent increase of WNV cases illustrates the importance of considering WNV in cases of meningoencephalitis, especially in immunocompromised patients, as described here. Proper education and communication and a revised diagnostic strategy will help to raise awareness and to detect future WNV infections.

Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response.

Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain.

Engaging local health research communities to enhance long-term capacity building in Brazil.

The '2019 Research Capacity Network (REDe) workshop series' was an initiative led by Brazil-based REDe coordinators and The Global Health Network (TGHN) in partnership with Brazilian researchers interested in arboviruses. This workshop initiative has provided crucial training to the local research community offering transferable skills to effectively respond to health emergencies, with an impact beyond arboviral diseases, as evidenced by further activities undertaken during the COVID-19 pandemic. The success of this approach resulted from several factors, especially the workshops' local leadership and the combination of in-person training with online sharing of the resources generated in the local language. Analytics data from REDe online platform evidenced the wider reach of the shared resources to a larger audience than the workshop attendees. Importantly, the impact of this approach extends beyond the workshop series per se, with workshop participants afforded access to wider training, career development and collaborative opportunities through REDe and TGHN platforms. In addition, this initiative design resulted in the development of new collaborations between the workshop leaders and other local researchers, who have been jointly writing research projects and applying for grants. As a result, REDe has become a highly dynamic community of practice for health researchers in the region, strengthening the research culture and improving connectivity. Here, we describe the design and implementation of this initiative and demonstrate the value of integrating local expertise, and a practical workshop series format with digital dissemination of research resources and training materials to generate a vibrant and robust community of practice.

Autochthonous Cases of Tick-Borne Encephalitis, Belgium, 2020.

We report 3 confirmed autochthonous tick-borne encephalitis cases in Belgium diagnosed during summer 2020. Clinicians should include this viral infection in the differential diagnosis for patients with etiologically unexplained neurologic manifestations, even for persons without recent travel history.

COVID-19 and its impact on the control of Aedes (Stegomyia) aegypti mosquito and epidemiological surveillance of arbovirus infections.

In American countries, simultaneously with the coronavirus disease 2019 (COVID-19) pandemic, epidemics caused by different arboviruses (dengue, chikungunya and Zika viruses) are occurring. In Mexico, several of the strategies to control the Aedes aegypti mosquito, which transmits arboviruses, involve the interaction of health personnel with the community. Due to the COVID-19 pandemic, social distancing and home confinement measures have been implemented. To obey these measures and avoid the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, the National Center for Preventive Programs and Disease Control (CENAPRECE) has presented the vector control strategy in the scenario of simultaneous dengue and COVID-19 transmission in Mexico. In this work, we mention the routine comprehensive mosquito control measures and describe the adaptations that have been made. Furthermore, we discuss the relevance of medical personnel training and supervision, especially focusing on the similarity of symptoms between both pathologies.

En países americanos, simultáneas a la pandemia de enfermedad por coronavirus 2019 (COVID-19) se están dando epidemias ocasionadas por diferentes arbovirus (del dengue, chikunguña y virus del Zika). En México, varias de las estrategias para control del mosquito Aedes aegypti, transmisor de arbovirus, involucran la interacción del personal salubrista y los moradores. Debido a la pandemia de COVID-19 se han implementado medidas de distanciamiento social y resguardo domiciliario. Para respetar estas medidas y evitar riesgo de contagio por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2), el Centro Nacional de Programas Preventivos y Control de Enfermedades (CENAPRECE) ha presentado la estrategia de control de vectores en el escenario de transmisión simultánea por dengue y COVID-19 en México. En este trabajo mencionamos las medidas habituales de manejo integral de mosquito y mencionamos las adaptaciones realizadas. De igual forma, discutimos la relevancia de la capacitación y la supervisión al personal médico, esto debido a la similitud entre la sintomatología entre ambas patologías.

[Ocular manifestations of viral diseases]. / Atteintes ophtalmologiques des infections virales.

Viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. Among them, ocular infections caused by herpesviruses are the most frequent. HSV-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the Western world, mainly because of corneal opacification caused by recurrences. For this reason, they may warrant long-term antiviral prophylaxis. Herpes zoster ophthalmicus, accounts for 10 to 20% of all shingles locations and can be associated with severe ocular involvement (keratitis, kerato-uveitis) of which a quarter becomes chronic/recurrent. Post herpetic neuralgias in the trigeminal territory can be particularly debilitating. Necrotizing retinitis caused by herpesviruses (HSV, VZV, CMV) are seldom, but must be considered as absolute visual emergencies, requiring urgent intravenous and intravitreal antiviral treatment. Clinical pictures depend on the immune status of the host. Adenovirus are the most frequent cause of infectious conjunctivitis. These most often benign infections are highly contagious and may be complicated by visually disabling corneal lesions that may last over months or years. Some arboviruses may be associated with inflammatory ocular manifestations. Among them, congenital Zika infections may cause macular or optic atrophy. Conjunctivitis is frequent during the acute phase of Ebola virus disease. Up to 15% of survivors present with severe chronic inflammatory ocular conditions caused by viral persistence in uveal tissues. Finally, COVID-19-associated conjunctivitis can precede systemic disease, or even be the unique manifestation of the disease. Utmost caution must be taken because of viral shedding in tears.

Strategies for the Production of Soluble Interferon-Alpha Consensus and Potential Application in Arboviruses and SARS-CoV-2.

Biopharmaceutical production is currently a multibillion-dollar industry with high growth perspectives. The research and development of biologically sourced pharmaceuticals are extremely important and a reality in our current healthcare system. Interferon alpha consensus (cIFN) is a non-natural synthetic antiviral molecule that comprises all the most prevalent amino acids of IFN-α into one consensus protein sequence. For clinical use, cIFN is produced in E. coli in the form of inclusion bodies. Here, we describe the use of two solubility tags (Fh8 and DsbC) to improve soluble cIFN production. Furthermore, we analyzed cIFN production in different culture media and temperatures in order to improve biopharmaceutical production. Our results demonstrate that Fh8-cIFN yield was improved when bacteria were cultivated in autoinduction culture medium at 30 °C. After hydrolysis, the recovery of soluble untagged cIFN was 58% from purified Fh8-cIFN molecule, fourfold higher when compared to cIFN recovered from the DsbC-cIFN, which achieved 14% recovery. The biological activity of cIFN was tested on in vitro model of antiviral effect against Zika, Mayaro, Chikungunya and SARS-CoV-2 virus infection in susceptible VERO cells. We show, for the first time, that cIFN has a potent activity against these viruses, being very low amounts of the molecule sufficient to inhibit virus multiplication. Thus, this molecule could be used in a clinical approach to treat Arboviruses and SARS-CoV-2.

Decreased dengue transmission in migrant worker populations in Singapore attributable to SARS-CoV-2 quarantine measures.

BACKGROUND: We examined the impact of SARS-CoV-2 social distancing and quarantine policies on dengue transmission in the general and migrant worker populations in Singapore. METHODS: We utilized all nationally reported dengue cases in the general and migrant worker populations from 1 January 2013 to 31 May 2020. A difference-in-difference identification strategy was used to determine the effects of social distancing and quarantine policies on reported dengue case counts over time, whilst controlling for weather patterns, seasonality, age and population size. RESULTS: A reduction of 4.8 dengue cases per age band among migrant workers was attributable to quarantine policies, corresponding to a total reduction of around 432 reported dengue cases over 10 weeks. In the general working population, an increase of 14.5 dengue cases per age band was observed, which corresponds to a total increase of around 1450 reported dengue cases in the same time period. There is an expected relative risk reduction in dengue transmission for the migrant worker population at 0.635 due to quarantine policy and a relative risk increase for the general working population due to social distancing policies at 0.685. CONCLUSIONS: Migrant workers experienced a reduced risk of dengue when they were confined to their dormitories as part of the COVID-19 social distancing measures. Our study highlights the vulnerability of migrant workers under normal working conditions.