Stepwise pathogenic evolution of Mycobacterium abscessus.

Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis, have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones.

The assessment of transmission efficiency and latent infection period in asymptomatic carriers of SARS-CoV-2 infection.

Few studies have focused on the transmission efficiency of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our follow-up study was performed on 147 asymptomatic carriers in Anhui Province. Of these, 50.0% were male, 50.3% were older than 40 years, 43.8% were farmers, and 68.7% were from the north of Anhui Province. 16 of the 147 asymptomatic carriers developed symptoms in the following 14 days of isolated observation, and were subsequently diagnosed as confirmed cases. The possible latent infection period was found to range from 1-5 days before onset, with a median time of 2 days. The second attack rate for the 16 confirmed cases who had transferred from being asymptomatic carriers was 9.7% (23/236 close contacts), while for the 131 asymptomatic carriers the rate was 2.6% (24/914 close contacts), showing a significant difference in second attack rate between the two groups (p＜0.001). Our study indicated that COVID-19 cases are contagious during the incubation period, and that close contact screening should be extended to include the incubation period. Our results also showed that the transmission efficiency for asymptomatic carriers was lower than that for confirmed case.

Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Tick-borne encephalitis (TBE) is one of the most important viral zoonosis transmitted by the bite of infected ticks. In this study, all tick-borne encephalitis virus (TBEV) E gene sequences available in GenBank as of June 2019 with known date of isolation (n = 551) were analyzed. Simulation studies showed that a sample bias could significantly affect earlier studies, because small TBEV datasets (n = 50) produced non-overlapping intervals for evolutionary rate estimates. An apparent lack of a temporal signal in TBEV, in general, was found, precluding molecular clock analysis of all TBEV subtypes in one dataset. Within all subtypes and most of the smaller groups in these subtypes, there was evidence of many medium- and long-distance virus transfers. These multiple random events may play a key role in the virus spreading. For some groups, virus diversity within one territory was similar to diversity over the whole geographic range. This is best exemplified by the virus diversity observed in Switzerland or Czech Republic. These two countries yielded most of the known European subtype Eu3 subgroup sequences, and the diversity of viruses found within each of these small countries is comparable to that of the whole Eu3 subgroup, which is prevalent all over Central and Eastern Europe. Most of the deep tree nodes within all three established TBEV subtypes dated less than 300 years back. This could be explained by the recent emergence of most of the known TBEV diversity. Results of bioinformatics analysis presented here, together with multiple field findings, suggest that TBEV may be regarded as an emerging disease.

Human Pythiosis: Emergence of Fungal-Like Organism.

Pythiosis is an emerging infectious disease caused by the aquatic oomycete Pythium insidiosum, a fungal-like organism. It is believed that P. insidiosum's zoospores, its infected form, play major role in pathogenesis. Vascular and ocular infections are the most common clinical manifestation in humans. It is difficult to establish the diagnosis given its relatively rarity and difficulty to distinguish P. insidiosum from other molds. Delay in diagnosis and treatment has been associated with poor outcomes. High index of suspicion is the key, particularly in thalassemia patients with arterial insufficiency and patients with fungal keratitis/endophthalmitis without improvement on antifungal therapy. Tissue culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The combination of radical surgery, antifungal agents, and immunotherapy has been recommended. It was previously believed that surgery with negative surgical margins was the essential to survive in vascular pythiosis; however, it was recently found that patients could have residual disease despite documented negative surgical margins as infected clot may be dislodged to proximal arterial sites prior to surgery. Serum ß-D-glucan (BG) has been used to monitor disease response after treatment initiation in vascular pythiosis. A significant decrease in BG levels within 2 weeks after surgery is indicative of the absence of residual infection. Unfortunately, monitoring tools for ocular pythiosis are not yet available. Itraconazole plus terbinafine have generally been used in P. insidiosum-infected patients; however, antibacterial agents, including azithromycin and linezolid, have also been used with favorable outcomes in ocular disease. Recently, azithromycin or clarithromycin plus doxycyclin were used in two relapsed vascular pythiosis patients with good outcomes.

Is Candida auris here to stay? An interview with Dimitrios Kontoyiannis.

In this exclusive interview, Dimitrios P Kontoyiannis discusses current mycology hot topic, Candida auris. With a focus on the current knowns and unknowns for the pathogenesis, resistance and transmission of this emerging fungal pathogen, in addition to a look at therapeutics and future perspectives. This interview was conducted by Ellen Colvin, Commissioning Editor of Future Microbiology. Dimitrios P Kontoyiannis is the Texas 4000 distinguished endowed professor and deputy head in the Division of Internal Medicine at MD Anderson Cancer Center in Houston (TX, USA). Dr Kontoyiannis has authored over 550 peer-reviewed manuscripts and has given over 330 lectures in national and international conferences and academic institutions in the USA and abroad. He is considered a leading mycology expert world-wide with an H index of 101 and over 43,000 citations. His research group is credited for many and sustained contributions to clinical, translational and experimental mycology. He is the recipient of many national and international awards and is the past president elect of Immunocompromised Host Society (2016-2018).

Existing and Emerging Blood-Borne Pathogens: Impact on the Safety of Blood Transfusion for the Hematology/Oncology Patient.

Despite measures to mitigate risk of transfusion-transmitted infections, emerging agents contribute to morbidity and mortality. We outline the epidemiology, risk mitigation strategies, and impact on patients for Zika virus, bacteria, Babesia, and cytomegalovirus. Nucleic acid testing of blood has reduced risk of Zika infection and reduced transfusion-transmitted risk of Babesia. Other collection and testing measures have reduced but not eliminated the risk of sepsis from bacterially contaminated blood components. Cytomegalovirus has almost been eliminated by high-efficiency leukoreduction, but residual transmissions are difficult to distinguish from community-acquired infections and additional antibody testing of blood may confer further safety of susceptible recipients.

Emergence of human infection with Jingmen tick virus in China: A retrospective study.

BACKGROUND: A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans. METHODS: We obtained skin-biopsy, blood and serum samples from patients with tick bites, and used high-throughput sequencing, in situ hybridisation, and serologic testing to diagnose and ascertain the cases of JMTV infection. FINDINGS: A JMTV strain was isolated from the tick Amblyomma javanense into an embryo-derived tick cell line. We obtained sustained passage of JMTV, and revealed that it was able to accumulate in salivary glands of experimentally infected ticks. Four JMTV-infected patients were identified by high-throughput sequencing of skin biopsies and blood samples. The virus replication in skin tissue was visualised by in situ hybridisation. The four patients all had an itchy or painful eschar at the site of tick bite, with or without lymphadenopathy. Immunohistochemical examination revealed remarkable local inflammation manifested as infiltration by neutrophils. Eight patients were identified by serological testing and showed more severe clinical manifestations. Two Ixodes persulcatus ticks detached from patients were positive for JMTV. All JMTV strains identified in this study formed a well-supported sub-lineage, distinct from those previously reported in China. Interpretation The public significance of JMTV should be highly concerning due to its potential pathogenicity for humans and efficient transmission by potential ticks. FUND: China Natural Science Foundation, State Key Research Development Programme, and United Kingdom Biotechnology and Biological Sciences Research Council.

West nile virus infections are here! are we prepared to face another flavivirus epidemic?

Abstract Emerging arthropod-borne viruses (arboviruses), such as chikungunya and Zika viruses, are a major threat to public health in countries like Brazil where biodiversity is high and medical care is sometimes precarious. West Nile fever is a disease caused by the West Nile Virus (WNV), an RNA virus belonging to the Flaviviridae family. It is transmitted by infected mosquitoes to numerous animals like birds, reptiles and mammals, including human and non-human primates. In the last decade, the number of reported cases of WNV infection in humans and animals has increased in the Americas. Circulation of WNV in forests and rural areas in Brazil has been detected based on serological surveys and, in 2014, the first case of West Nile fever was confirmed in a patient from Piauí State. In 2018, the virus was isolated for the first time from a horse from a rural area in the state of Espírito Santo presenting with a neurological disorder; this raises the possibility that other cases of WNV encephalitis may have occurred without clinical recognition and without laboratory diagnosis by specific assays. The imminent WNV outbreak poses a challenge for Brazilian clinicians and researchers. In this review, we summarize the basic biological and ecological characteristics of this virus and the clinical presentation and treatment of febrile illnesses caused by WNV. We also discuss the epidemiological aspects, prophylaxis of WNV infections, and monitoring strategies that could be applied in the possibility of a WNV outbreak in Brazil.

Haematology patients and the risk of transfusion transmitted infection.

A 2014 study by NHS Blood and Transplant indicated that over one quarter of red cells were transfused to patients with haematological conditions. For platelet components, the figure is higher. Certain diagnostic groups, such as haemoglobinopathies, myelodysplastic syndromes and some haemato-oncology patients, receive multiple transfusion episodes, either over long periods, or more intensively over shorter periods. Haematology patients account for the majority of the multi-transfused population. The risk of transfusion-transmitted infection (TTI) increases with number of donor exposures, and the consequences of TTI are often more significant in immunosuppressed individuals. Historically, use of pooled plasma products in patients with clotting disorders resulted in widespread transmission of hepatitis B virus, hepatitis C virus and human immunodeficiency virus before effective screening and viral inactivation methods were introduced.

Taenia solium in Europe: Still endemic?

The pork tapeworm, Taenia solium, causes an important economic and health burden, mainly in rural or marginalized communities of sub-Saharan Africa, Asia, and Latin-America. Although improved pig rearing conditions seem to have eliminated the parasite in most Western European countries, little is known about the true endemicity status of T. solium throughout Europe. Three recent reviews indicate that autochthonous human T. solium taeniasis/cysticercosis may be possible in Europe, but that current peer-reviewed literature is biased towards Western Europe. Officially reported data on porcine cysticercosis are highly insufficient. Favourable conditions for local T. solium transmission still exist in eastern parts of Europe, although the ongoing integration of the European Union is speeding up modernisation and intensification of the pig sector. Further evidence is urgently needed to fill the gaps on the European T. solium endemicity map. We urge to make human cysticercosis notifiable and to improve the reporting of porcine cysticercosis.

Arboviruses emerging in Brazil: challenges for clinic and implications for public health / Arboviroses emergentes no Brasil: desafios para a clínica e implicações para a saúde pública

ABSTRACT Arboviruses have been emerging in different parts of the world due to genetic changes in the virus, alteration of the host and vector population dynamics, or because of anthropogenic environmental factors. These viruses’ capacity for adaptation is notable, as well as the likelihood of their emergence and establishment in new geographic areas. In Brazilian epidemiologic scenario, the most common arboviruses are DENV, CHIKV, and ZIKV, although others may spread in the country. Little is yet known of the impact of viral co-circulation, which would theoretically result in more intense viremia or other immunological alterations that could trigger autoimmune diseases, such as Guillain-Barré syndrome. The impact on morbidity and mortality intensifies as extensive epidemics lead to a high number of affected individuals, severe cases, and implications for health services, mainly due to the absence of treatment, vaccines, and effective prevention and control measures.

RESUMO Notifica-se a emergência de arboviroses em diferentes regiões do planeta em decorrência de mudanças genéticas no vírus, alteração da dinâmica populacional de hospedeiros e vetores ou por fatores ambientais de origem antropogênica. É notável a capacidade de adaptação desses vírus e a possibilidade de emergirem e se estabelecerem em novas áreas geográficas. No contexto epidemiológico brasileiro, os arbovírus de maior circulação são DENV, CHIKV e ZIKV, embora existam outros com potencial de disseminação no País. O impacto da cocirculação viral ainda é pouco conhecido, a qual teoricamente resultaria em viremias mais intensas ou outras alterações imunológicas que poderiam ser o gatilho para doenças autoimunes, como a síndrome de Guillain-Barré. O impacto na morbidade e mortalidade se intensifica à medida que extensas epidemias pressupõem grande número de indivíduos acometidos, casos graves e implicações sobre os serviços de saúde, principalmente diante da ausência de tratamento, vacinas e medidas efetivas de prevenção e controle.

Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium.

Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

Rapid evolutionary response to a transmissible cancer in Tasmanian devils.

Although cancer rarely acts as an infectious disease, a recently emerged transmissible cancer in Tasmanian devils (Sarcophilus harrisii) is virtually 100% fatal. Devil facial tumour disease (DFTD) has swept across nearly the entire species' range, resulting in localized declines exceeding 90% and an overall species decline of more than 80% in less than 20 years. Despite epidemiological models that predict extinction, populations in long-diseased sites persist. Here we report rare genomic evidence of a rapid, parallel evolutionary response to strong selection imposed by a wildlife disease. We identify two genomic regions that contain genes related to immune function or cancer risk in humans that exhibit concordant signatures of selection across three populations. DFTD spreads between hosts by suppressing and evading the immune system, and our results suggest that hosts are evolving immune-modulated resistance that could aid in species persistence in the face of this devastating disease.

Enfermedades infecciosas emergentes y reemergentes: información actualizada / Emerging and re-emerging infectious diseases: updated information

A fines del siglo XX, una gran diversidad de factores contribuyeron a la aparición de enfermedades infecciosas emergentes, con importante impacto en la salud pública. Estas enfermedades, en general, se caracterizan por ser de reciente aparición, provocar una inusual incidencia en una población o área geográfica, o reaparecer luego de haber cesado su actividad por largo tiempo(1). Algunas enfermedades emergentes, como VIH/SIDA, persisten por años, en tanto que otras, luego de su aparición, duran períodos limitados. Múltiples factores, además del agente infeccioso, intervienen en el complejo proceso que determina la emergencia de enfermedades infecciosas. Constantemente, miles de microorganismos potencialmente patógenos se diseminan en nuevas áreas geográficas, pero solo unos pocos llegan a sobrevivir y causar enfermedades, favorecidos por condicionantes socioeconómicas, ambientales y ecológicas. Este fenómeno mundial requiere una vigilancia epidemiológica constante, con una infraestructura nacional y regional que asegure una alerta temprana frente a la emergencia o reemergencia de esas enfermedades.

In the late 20th century, several different factors contributed to the appearance of emerging infectious diseases that had a great impact on public health. In general, these diseases are characterized by appearing for the first time, they rapidly increase in incidence in certain populations or geographical area, or they have been known for some time although they have disappeared for a long time. A few infectious diseases like HIV/AIDS have persisted for several years, while others, after appearing, last limited periods of time. Multiple factors, apart from the infectious agent, take part in the complex process that results in the emergence of an infectious disease. Thousands of potentially pathogenic microorganisms are constantly disseminated in new geographical areas, although just a few manage to survive and cause diseases, favored by social, economic, environment and ecologic factors. This global phenomenon requires continuous epidemiological surveillance, with a national and regional infrastructure that enables an early alert upon these diseases that emerge or re-emerge.

No final do século XX, muitos fatores diferentes contribuíram para o surgimento de doenças infecciosas emergentes, com importante impacto sobre a saúde pública. De maneira geral, estas doenças se caracterizam por haver surgido recentemente, provocar uma incidência pouco comum em uma população ou área geográfica, ou reaparecer depois de haver cessado sua atividade por um tempo prolongado (1). Algumas doenças emergentes, como VIH/SIDA, persistem por anos, enquanto outras têm uma duração limitada. Além do agente infeccioso, muitos outros fatores intervêm no complexo processo que determina o surgimento de doenças infecciosas. Constantemente, milhares de micro-organismos potencialmente patógenos se disseminam em novas áreas geográficas, mas somente poucos são capazes de sobreviver e causar doenças, favorecidos por condicionantes socioeconômicos, ambientais e ecológicos. Este fenômeno mundial requer uma vigilância epidemiológica constante, com una infraestrutura nacional e regional que garanta um alerta precoce frente à emergência ou reemergência de essas doenças.

[Description of the process of preparation and response of local health authorities facing the introduction of the Chikungunya virus in Colombia, 2014]. / Caracterización del proceso de preparación y respuesta de entidades territoriales de salud ante la introducción del virus Chikungunya, Colombia, 2014.

Objective To describe the process of preparation and response of local health authorities in key public health issues while facing the introduction stage of an unusual virus: Chikungunya in Colombia in 2014. Methods A cross-sectional study was conducted using a survey that was developed for this study and sent to Public Health coordinators and to the person in charge of vector borne-diseases in the country's territorial entities. Results 23 out of the 35 territories at risk from the transmission of Chikungunya agreed to answer the survey. A global review of the survey scores for each evaluated section shows better performances in the areas of knowledge management, comprehensive patient care, epidemiological intelligence, and health promotion. According to the results of this study, the epidemiological surveillance system during the Chikungunya epidemic had a low acceptability and flexibility, possibly contributing to the underreporting of cases. Conclusions In general, knowledge and implementation by local authorities of the Integrated Health Strategy- EGI (Estrategia de Gestión Integral, by its Spanish acronym)- for vector-borne diseases was evident from the themes evaluated in this study. However, it is necessary to reinforce the communication of risks, laboratory, and outbreak and contingencies management areas faced during the introduction of new viruses.