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Zika virus - Top 30 Publications

Zika virus - the glamour of a new illness, the practical abandonment of the mothers and new evidence on uncertain causality.

Challenges of Vaccine Development for Zika Virus.

The emergence of outbreaks of Zika virus (ZIKV) in Brazil in 2015 was associated with devastating effects on fetal development and prompted a world health emergency and multiple efforts to generate an effective vaccine against infection. There are now more than 40 vaccine candidates in preclinical development and six in clinical trials. Despite similarities with other flaviviruses to which successful vaccines have been developed, such as yellow fever virus and Japanese Encephalitis virus, there are unique challenges to the development and clinical trials of a vaccine for ZIKV.

RETREG1 (FAM134B): a new player in human diseases: 15 years after the discovery in cancer.

FAM134B (family with sequence similarity 134, member B) / RETREG1 and its functional roles are relatively new in human diseases. This review aimed to summarize various functions of FAM134B since our first discovery of the gene in 2001. The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis. Absence or non-functional expression of FAM134B protein impairs ER-turnover and thereby is involved in the pathogenesis of some human diseases. FAM134B inhibition contributes to impair proteostasis in the ER due to the accumulation of misfolded or aggregated proteins, which in turn leads to compromised neuronal survival and progressive neuronal degenerative diseases. Mutations in FAM134B associated with hereditary sensory and autonomic neuropathy type IIB (HSAN IIB). Selective cleavage of FAM134B by Dengue, Zika and West Nile virus encoded protease NS2B3 leads to the increased production of infection units, whereas upregulation of FAM134B inhibits viral replication. In cancer, FAM134B acts as a tumour suppressor and inhibit cancer growth both in-vitro and in-vivo. Pharmacological upregulation of FAM134B resulted in reduced cancer cell growth and proliferation. In addition, FAM134B mutations are common in patients with colorectal adenocarcinoma and oesophageal squamous cell carcinoma. These mutations and expression changes of FAM134B were associated with the biological aggressiveness of these cancers. FAM134B also plays a role in allergic rhinitis, vascular dementia and identification of stem cells. Taken together, information available in the literature suggests that FAM134B plays critical roles in human diseases, by interacting with different biological and chemical mediators, which are primarily regulated by ER turnover. This article is protected by copyright. All rights reserved.

Zika virus reservoirs: Implications for transmission, future outbreaks, drug and vaccine development.

Zika virus (ZIKV) was recently declared as a 'Global Health Emergency' by the World Health Organization. Various tissue reservoirs of ZIKV in infected humans and animals models have been observed, the implications of which are not known. Compared to other Flaviviruses, sexual transmission and persistence in the genitourinary tract seem to be unique to ZIKV. ZIKV persistence and shedding in bodily secretions (e.g. saliva, semen) is a concern for potential disease spread and could pose challenges in diagnosis, regulatory guidelines and drug/vaccine development. Murine and non-human primate models could be useful to study the role of tissue reservoirs in the development of prophylactic or therapeutic strategies. There is a need for meta-analysis of the ZIKV infection and virus shedding data from infected patients and ZIKV animal models, and additional research is needed to fully comprehend the long term implications of tissue reservoirs on ZIKV disease pathogenesis and biology.

In Silico Validation of D7 Salivary Protein-derived B- and T-cell Epitopes of Aedes aegypti as Potential Vaccine to Prevent Transmission of Flaviviruses and Togaviruses to Humans.

Mosquito (Aedes aegyptii) salivary proteins play a crucial role in facilitating viral transmission from vector-to-host due to their role in facilitating the "blood meal" of the vector. Three main proteins, D7, aegyptin and Sialokinin play a role in this process. Using in-silico programs, we identified B- and T-cell epitopes in the mosquito salivary proteins D7 long and short form. T-cell epitopes with high affinity to the most prevalent HLA MHC class-I supertypes among different population groups was chosen. It is our postulate that these epitopes could be successful in eliciting B and T cell responses, which would decrease the vector blood meal efficiency and hence protect against host infection by certain viruses. These include causative agents like Dengue viruses, Chikungunya virus, Zika and Yellow fever viruses. These viruses are of major public health importance in several countries in the Americas, Asia and Africa. Experimental evidence exists in previously published literature showing the protective effect of antibodies to certain salivary proteins in susceptible hosts. A novel approach of immunizing humans against the vector proteins to reduce transmission of viruses is now under investigation in several laboratories. We have identified the following two B cell epitopes LAALHVTAAPLWDAKDPEQF one from D7L and the other TSEYPDRQNQIEELNKLCKN from D7S. Likewise, two T cell epitopes MTSKNELDV one from D7L and the other YILCKASAF from D7S with affinity to the predominant MHC class-I supertypes were identified towards evaluation as potential vaccine.

Zika Virus and the Rio Olympic Games.

To evaluate the impact of Zika virus on preparation and management of the New Zealand (NZ) Olympic team.

Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials.

The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins.

Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials.

A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings.

The immune strategies of mosquito Aedes aegypti against microbial infection.

Yellow fever mosquito Aedes aegypti transmits many devastating arthropod-borne viruses (arboviruses), such as dengue virus, yellow fever virus, Chikungunya virus, and Zika virus, which cause great concern to human health. Mosquito control is an effective method to block the spread of infectious diseases. Ae. aegypti uses its innate immune system to fight against arboviruses, parasites, and fungi. In this review, we briefly summarize the recent findings in the immune response of Ae. aegypti against arboviral and entomopathogenic infections. This review enriches our understanding of the mosquito immune system and provides evidence to support the development of novel mosquito control strategies.

Assessing the zoonotic potential of arboviruses of African origin.

Several African arboviruses have emerged over the past decade in new regions where they caused major outbreaks in humans and/or animals including West Nile virus, Chikungunya virus and Zika virus. This raise questions regarding the importance of less known zoonotic arboviruses in local epidemics in Africa and their potential to emerge internationally. Syndromic surveillance in animals may serve as an early warning system to detect zoonotic arbovirus outbreaks. Rift Valley fever and Wesselsbronvirus are for example associated with abortion storms in livestock while West Nile-virus, Shuni virus and Middelburg virus causes neurological disease outbreaks in horses and other animals. Death in birds may signal Bagaza virus and Usutu virus outbreaks. This short review summarise data on less known arboviruses with zoonotic potential in Africa.

Differences in prevalence of symptomatic Zika virus infection by age and sex-Puerto Rico, 2016.

During the Zika virus (ZIKV) outbreak in Puerto Rico in 2016, non-pregnant women aged 20-39 years were disproportionately identified with ZIKV disease. We used household-based cluster investigations to determine if this disparity was associated with age- or sex-dependent differences in the rate of ZIKV infection or reporting symptoms.

Novel Wolbachia-transinfected Aedes aegypti mosquitoes possess diverse fitness and vector competence phenotypes.

Wolbachia pipientis from Drosophila melanogaster (wMel) is an endosymbiotic bacterium that restricts transmission of human pathogenic flaviviruses and alphaviruses, including dengue, Zika, and chikungunya viruses, when introduced into the mosquito vector Aedes aegypti. To date, wMel-infected Ae. aegypti have been released in field trials in 5 countries to evaluate the effectiveness of this strategy for disease control. Despite the success in establishing wMel-infected mosquitoes in wild populations, and the well-characterized antiviral capabilities of wMel, transinfecting different or additional Wolbachia strains into Ae. aegypti may improve disease impact, and perhaps more importantly, could provide a strategy to account for the possible evolution of resistant arboviruses. Here, we report the successful transinfection of Ae. aegypti with the Wolbachia strains wMelCS (D. melanogaster), wRi (D. simulans) and wPip (Culex quinquefasciatus) and assess the effects on Ae. aegypti fitness, cytoplasmic incompatibility, tissue tropism and pathogen blocking in a laboratory setting. The results demonstrate that wMelCS provides a similar degree of protection against dengue virus as wMel following an infectious blood meal, and significantly reduces viral RNA levels beyond that of wMel following a direct challenge with infectious virus in mosquitoes, with no additional fitness cost to the host. The protection provided by wRi is markedly weaker than that of wMelCS, consistent with previous characterisations of these lines in Drosophila, while wPip was found to substantially reduce the fitness of Ae. aegypti. Thus, we determine wMelCS as a key candidate for further testing in field-relevant fitness tests and viremic blood feeding challenges in a clinical setting to determine if it may represent an alternative Wolbachia strain with more desirable attributes than wMel for future field testing.

Experimental Zika Virus Inoculation in a New World Monkey Model Reproduces Key Features of the Human Infection.

A monkey model of Zika virus (ZIKV) infection is urgently needed to better understand transmission and pathogenesis, given its proven association with fetal brain defects in pregnant women and acute neurological illness. Here we experimentally infected 4 male marmosets with ZIKV (prototype 1947 African strain) and monitored them clinically with sampling of various body fluids and tissues for nearly 3 months. We show that the course of acute infection with ZIKV in these New World monkeys resembles the human illness in many respects, including (1) lack of apparent clinical symptoms in most cases, (2) persistence of the virus in body fluids such as semen and saliva for longer periods of time than in serum, and (3) generation of neutralizing antibodies as well as an antiviral immunological host response. Importantly, ZIKV-infected saliva samples (in addition to serum) were found to be infectious, suggesting potential capacity for viral transmission by the oral route. Re-challenge of a previously infected marmoset with a contemporary outbreak strain SPH2015 from Brazil resulted in continued protection against infection, no viral shedding, and boosting of the immune response. Given the key similarities to human infection, a marmoset model of ZIKV infection may be useful for testing of new drugs and vaccines.

Experimental adaptive evolution of SIVcpz to pandemic HIV-1 using a humanized mouse model.

HIV-1, the causative agent of AIDS, is originated from SIVcpz, the chimpanzee precursor of the human virus, approximately 100 years ago. This indicates that HIV-1 has emerged through the cross-species transmission of SIVcpz from chimpanzees to humans. However, it remains unclear how SIVcpz has evolved into pandemic HIV-1 in humans. To address this question, we inoculated three SIVcpz (MB897, EK505, and MT145), four pandemic HIV-1 (NL4-3, NLCSFV3, JRCSF and AD8) and 2 non-pandemic HIV-1 (YBF30 and DJO0131) strains. Humanized mice infected with SIVcpz strain MB897, a virus phylogenetically similar to pandemic HIV-1, exhibited a comparable peak viral load to that of mice infected with pandemic HIV-1, while peak viral loads of mice infected with SIVcpz strains EK505 or MT145 as well as non-pandemic HIV-1 strains were significantly lower. These results suggest that SIVcpz strain MB897 is pre-adapted to humans when compared to the other SIVcpz strains. Moreover, viral RNA sequencing of MB897-infected humanized mice identified a nonsynonymous mutation in env, G413R substitution in gp120. The infectivity of the gp120 G413R mutant of MB897 was significantly higher than that of parental MB897. Furthermore, we demonstrated that the gp120 G413R mutant of MB897 augments the capacity for viral replication in both in vitro cell cultures and humanized mice. Taken together, this is the first experimental investigation to use an animal model to demonstrate a gain-of-function evolution of SIVcpz into pandemic HIV-1.ImportanceFrom the mid-20th century, humans are exposed to the menace of viral infectious diseases such as SARS coronavirus, Ebola virus and Zika virus. These outbreaks of emerging/re-emerging viruses can be triggered by cross-species viral transmission from wild animals to humans or zoonoses. HIV-1, the causative agent of AIDS, was emerged by the cross-species transmission of SIVcpz, the HIV-1 precursor in chimpanzee, around 100 years ago. However, the process by which SIVcpz evolved to become HIV-1 in humans remains unclear. By using a hematopoietic stem cell-transplanted humanized mouse model, here we experimentally recapitulate the evolutionary process of SIVcpz to become HIV-1. We provide evidence suggesting that a strain of SIVcpz, MB897, has pre-adapted to infect humans comparing to other SIVcpz strains. We further demonstrate a gain-of-function evolution of SIVcpz in infected humanized mice. Our study reveals that pandemic HIV-1 has emerged through at least two steps: preadaptation and subsequent gain-of-function mutations.

Suppression of Zika virus infection and replication in endothelial cells and astrocytes by PKA inhibitor PKI 14-22.

The recent outbreak of Zika virus (ZIKV), a re-emerging flavivirus, and its associated neurological disorders, such as Guillain-Barré (GB) syndrome and microcephaly, have generated an urgent need for developing effective ZIKV vaccines and therapeutic agents. Here, we used human endothelial cells and astrocytes, both of which represent key cell types for ZIKV infection, to identify potential inhibitors for ZIKV replication. Because several pathways, including AMP-activated protein kinase (AMPK), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) signaling pathways, have been reported to play important roles in flavivirus replication, we tested inhibitors or agonists of these pathways for their effects on ZIKV replication. We identified PKA inhibitor, PKI 14-22 (PKI), as a potent inhibitor of ZIKV replication. PKI effectively suppressed the replication of ZIKV from both African and Asian/American lineages with high efficiency and minimal cytotoxicity. While ZIKV infection did not induce PKA activation, endogenous PKA activity was essential for supporting ZIKV replication. Interestingly, in addition to PKA, PKI also inhibited other unknown target(s) to block ZIKV replication. PKI inhibited ZIKV replication at the post-entry stage by preferentially affecting negative-sense RNA synthesis as well as viral protein translation. Together, these results have identified a potential inhibitor of ZIKV replication, which could be further explored for future therapeutic application.ImportanceThere is an urgent need to develop effective vaccines and therapeutic agents against Zika virus (ZIKV) infection, a re-emerging flavivirus associated with neurological disorders including Guillain-Barré (GB) syndrome and microcephaly. By screening for inhibitors of several cellular pathways, we have identified PKA inhibitor PKI 14-22 (PKI) as a potent inhibitor of ZIKV replication. We have shown that PKI effectively suppresses the replication of ZIKV of all the strains tested with minimal cytotoxicity in human endothelial cells and astrocytes, two key cell types of ZIKV infection. Furthermore, we have shown that PKI inhibits ZIKV negative-sense RNA synthesis and viral protein translation. This study has identified a potent inhibitor of ZIKV infection, which could be further explored for future therapeutic application.

Re: Letter to the Editor of Public Health in response to 'Public sentiment and discourse about Zika virus on Instagram'.

Re: 'Public sentiment and discourse about Zika virus on Instagram'.

Production of Monoclonal Antibody That Recognizes Zika Virus and Other Flaviviruses in Serum-Free Conditions.

With the recent outbreaks of Zika and Dengue virus infections in various countries worldwide, production of vaccines or diagnostic kits is an urgent public health demand. Production of a monoclonal antibody (mAb) that specifically binds to a common antigen shared by the Flavivirus genus will be necessary for new diagnostic kits or characterization and viral identity tests during vaccine development. This study aimed to cultivate, in serum-free conditions, the 4G2 hybridoma that produces an mAb, which recognizes a shared epitope from the Flavivirus genus. We compared 4G2 hybridoma growth and biochemical profiles between cells cultivated in batch mode over 10 days in roller bottles containing Dulbecco's modified Eagle's medium high glucose containing 10% fetal bovine serum medium or hybridomas directly adapted to Ex-Cell serum-free medium. Cellular parameters such as specific growth rate (μ), maximum cell concentration, specific l-lactate, and glucose and IgG rates were evaluated. Thereafter, we also compared total mAb volumetric productivity, purification yield, and mAb staining of Vero cells infected with Zika and Dengue-2 virus. Direct adaptation to serum-free conditions did not change hybridoma growth rate and mAb production under the conditions tested. Instead, serum-free mAb purification showed a higher yield with no alterations on mAb structure or mAb staining of Zika and Dengue Vero-infected cells.

Profile of demand and Continuous Cash Benefits (BCP) granted to children diagnosed with microcephaly in Brazil.

The Brazilian Federal Constitution of 1988 introduced the Continuous Cash Benefits (BCP), allowing the inclusion of people with disabilities. This is a descriptive study with aggregate municipal data about the time and geographic distribution of the incidence of microcephaly related to the Zika virus in Brazil and data of the BCP grants to children diagnosed with microcephaly. Data on the demand and BCP grants to children with microcephaly since 2009 are shown. Cases of microcephaly and/or central nervous system disorders were obtained from the Ministry of Health and totaled 2,366 confirmed cases from January 1, 2015 to December 31, 2016. The historical series of BCP granted from 2009 to 2016 was based on data from the National Institute of Social Security and showed, until 2014, a baseline with an average of 200 annual benefits for children younger than 48 months with microcephaly. In 2016, grants increased eight times, reaching 1,603 benefits granted to children of 731 municipalities spread in the 27 States. The Northeast accounted for 73% of the BCPs granted, however, this was less than 65% of the demand for incident cases. The implementation of the integrated referral system, including active search, should be strengthened to ensure access to all children entitled to BCP.

Corrigendum: Serum Metabolic Alterations upon Zika Infection.

[This corrects the article on p. 1954 in vol. 8, PMID: 29067015.].

Dengue in Rio Grande do Sul, Brazil: 2014 to 2016.

The first autochthonous dengue case in Rio Grande do Sul (RS), Southern Brazil, occurred in 2007. In 2008 and 2009, only imported cases were reported in RS, but from 2010 to 2013, reports of autochthonous infections increased significantly. This study analyzes and discusses laboratory, demographic, and clinical data regarding dengue cases in RS, from 2014 to 2016. This study analyzed 13,420 serum samples from notified patients with suspicion of dengue fever in RS from 2014 to 2016. Seasonality of positive cases, viral serotypes, and clinical and epidemiological aspects were analyzed. There was no difference in gender (P = .4); dengue fever occurred mainly in adults, with similar distribution among age groups. The number of dengue virus (DENV) cases increased from 89 cases in 2014 to 2518 in 2016. Dengue virus 1 was the most prevalent circulating serotype during this period (97.5% of cases). Dengue virus infections show peaks in March and April (late summer and early autumn), after periods of high temperatures and rainfall. In 2014, dengue cases were concentrated in the northwestern and eastern regions of RS, and in 2015 and 2016, the northern region also confirmed a high number of cases. With increase in DENV circulation in RS, a rise in the number of autochthonous infections was also observed, mainly in highly urbanized areas. This study revealed that circulation of DENV in RS increased significantly in 2015 and 2016, with a rise in the number of autochthonous infections and cocirculation with Chikungunya and Zika viruses, recently introduced into RS.

Neuroimaging findings associated with congenital Zika virus syndrome: case series at the time of first epidemic outbreak in Pernambuco State, Brazil.

This study aimed to describe the prenatal and postnatal neuroimaging and clinical findings in a clinical series following congenital Zika virus syndrome during the first epidemic Zika virus (ZIKV) outbreak in the State of Pernambuco, Brazil.

One Health Perspectives on Emerging Public Health Threats.

Antimicrobial resistance and emerging infectious diseases, including avian influenza, Ebola virus disease, and Zika virus disease have significantly affected humankind in recent years. In the premodern era, no distinction was made between animal and human medicine. However, as medical science developed, the gap between human and animal science grew deeper. Cooperation among human, animal, and environmental sciences to combat emerging public health threats has become an important issue under the One Health Initiative. Herein, we presented the history of One Health, reviewed current public health threats, and suggested opportunities for the field of public health through better understanding of the One Health paradigm.

Targets and Receptor of Sexual Transmission of Zika Virus.

Psychological Distress and Zika, Dengue and Chikungunya Symptoms Following the 2016 Earthquake in Bahía de Caráquez, Ecuador.

On 16 April 2016, a 7.8 magnitude earthquake struck coastal Ecuador, resulting in significant mortality and morbidity, damages to infrastructure, and psychological trauma. This event coincided with the first outbreak of Zika virus (ZIKV) and co-circulation with dengue virus (DENV) and chikungunya virus (CHIKV). We tested whether the degree of psychological distress was associated with the presence of suspected DENV, CHIKV, ZIKV (DCZ) infections three months after the earthquake. In July 2016, 601 household members from four communities in Bahía de Caráquez, Manabí Province, Ecuador, were surveyed in a post-disaster health evaluation. Information was collected on demographics, physical damages and injuries, chronic diseases, self-reported psychological distress, and DCZ symptoms. We calculated the prevalence of arbovirus and distress symptoms by community. ANOVA was used to compare the mean number of psychological distress symptoms between people with versus without suspected DCZ infections by age, gender, community and the need to sleep outside of the home due to damages. The prevalence of suspected DCZ infections was 9.7% and the prevalence of psychological distress was 58.1%. The average number of psychological distress symptoms was significantly higher among people with suspected DCZ infections in the periurban community of Bella Vista, in women, in adults 40-64 years of age and in individuals not sleeping at home (p < 0.05). The results of this study highlight the need to investigate the interactions between psychological distress and arboviral infections following natural disasters.

Post-chikungunya chronic inflammatory rheumatism: Follow-up of cases after 1 year of infection in Tolima, Colombia.

Chronic Inflammatory Rheumatism (CIR) is one of the recognized and increasingly reported consequence post-chikungunya infection (pCHIK) in Colombia and Latin America.

Phylodynamic applications in 21st century global infectious disease research.

Phylodynamics, the study of the interaction between epidemiological and pathogen evolutionary processes within and among populations, was originally defined in the context of rapidly evolving viruses and used to characterize transmission dynamics. The concept of phylodynamics has evolved since the early 21st century, extending its reach to slower-evolving pathogens, including bacteria and fungi, and to the identification of influential factors in disease spread and pathogen population dynamics.

Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection.

Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti, which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.

Lymphatic system and gut microbiota affect immunopathology of neuroinflammatory diseases, including multiple sclerosis, neuromyelitis optica and Alzheimer's disease.

Microbial infections lead to neurological damages either by direct infection in the nervous tissues or by uncontrolled immune responses (immunopathology). For example, in Zika virus infection, microcephaly can be caused by the former, i.e., direct viral infection in the brain, while Guillain-Barré syndrome (GBS) seems to be antibody-mediated immunopathology. Although a variety of factors affect immunopathology, two essential systems maintaining whole-body homeostasis had long been neglected: 1) the lymphatic system and 2) microbiota. Only recently, the role of the lymphatic system in immunopathology is beginning to be clarified. During infection, increased lymphatic flow limits edema and prevent tissue dendritic cell retention, while lymphostasis can lead to chronic inflammation. The role of gut microbiota, particularly bacterial community, in immunopathology has also been clarified recently; "bad bacteria" are proposed to exacerbate any immunopathology. For example, Helicobacter pylori is associated with not only gastritis but also extra-intestinal diseases, including neuromyelitis optica (NMO) and Alzheimer's disease. However, H. pylori and another bad bacterium Clostridium perfringens type A have been proposed to be protective against multiple sclerosis (MS). The above discrepancy on the roles of microbiota can be attributed to several conflicting factors, such as oversimplification, methodology, and taxonomy, which are summarized as "10 pitfalls of microbiota studies."

Zika virus in semen: a prospective cohort study of symptomatic travellers returning to Belgium.

To prospectively monitor Zika viral loads in semen from Belgian travellers with confirmed Zika virus infection, who returned from the Americas during the 2016 Zika virus epidemic.