GENETIC DIVERSITY OF THE CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUSES CIRCULATING IN THE WORLD (REVIEW)

Вирус Конго-Крымской геморрагической лихорадки является возбудителем тяжелой клещевой, часто смертельной, Конго-Крымской геморрагической лихорадки, которая широко распространена во всем мире. Передача вируса Конго-Крымской геморрагической лихорадки к человеку происходит через укус клеща, раздавливание зараженных клещей или контакт с инфицированной кровью человека. Миграция вируса способна через клещей с животными и перелетных птиц, в связи с чем имеется возможность исследования географического распространения посредством генетического анализа. В этом обзоре мы стремимся обобщить самые последние данные о генетическом разнообразии вирусов Конго-Крымской геморрагической лихорадки, циркулирующих в мире. Временной и пространственный анализ многообразия штаммов вируса может послужить ключевым фактором для лучшего понимания связи серопозитивности и уровня летальности. The Crimean-Congo hemorrhagic fever virus is the causative agent of severe tick-borne, often fatal, zoonotic Crimean-Congo hemorrhagic fever, which is widespread throughout the world. Transmission of the Crimean-Congo hemorrhagic fever virus to humans occurs through a tick bite, crushing of infected ticks or contact with infected host blood. The migration of the virus is possible through ticks with animals and migratory birds, and therefore it is possible to study the geographical distribution through genetic analysis. In this review, we aim to summarize the latest data on the genetic diversity of the Crimean-Congo hemorrhagic fever viruses circulating in the world. The temporal and spatial analysis of the diversity of virus strains can serve as a key factor for a better understanding of the relationship between seropositivity and the mortality rate.

ABO Blood Groups Do Not Predict Schistosoma mansoni Infection Profiles in Highly Endemic Villages of Uganda

Schistosoma mansoni is a parasite which causes significant public-health issues, with over 240 million people infected globally. In Uganda alone, approximately 11.6 million people are affected. Despite over a decade of mass drug administration in this country, hyper-endemic hotspots persist, and individuals who are repeatedly heavily and rapidly reinfected are observed. Human blood-type antigens are known to play a role in the risk of infection for a variety of diseases, due to cross-reactivity between host antibodies and pathogenic antigens. There have been conflicting results on the effect of blood type on schistosomiasis infection and pathology. Moreover, the effect of blood type as a potential intrinsic host factor on S. mansoni prevalence, intensity, clearance, and reinfection dynamics and on co-infection risk remains unknown. Therefore, the epidemiological link between host blood type and S. mansoni infection dynamics was assessed in three hyper-endemic communities in Uganda. Longitudinal data incorporating repeated pretreatment S. mansoni infection intensities and clearance rates were used to analyse associations between blood groups in school-aged children. Soil-transmitted helminth coinfection status and biometric parameters were incorporated in a generalised linear mixed regression model including age, gender, and body mass index (BMI), which have previously been established as significant factors influencing the prevalence and intensity of schistosomiasis. The analysis revealed no associations between blood type and S. mansoni prevalence, infection intensity, clearance, reinfection, or coinfection. Variations in infection profiles were significantly different between the villages, and egg burden significantly decreased with age. While blood type has proven to be a predictor of several diseases, the data collected in this study indicate that it does not play a significant role in S. mansoni infection burdens in these high-endemicity communities.

Host Blood Gene Signatures Can Detect the Progression to Severe and Cerebral Malaria

Malaria is a major international public health problem that affects millions of patients worldwide especially in sub-Saharan Africa. Although many tests have been developed to diagnose malaria infections, we still lack reliable diagnostic biomarkers for the identification of disease severity, especially in endemic areas where the diagnosis of cerebral malaria is very difficult and requires the exclusion of all other possible causes. Previous host and pathogen transcriptomic studies have not yielded homogenous results that can be harnessed into a reliable diagnostic tool. Here we utilized a multi-cohort analysis approach using machine-learning algorithms to identify blood gene signatures that can distinguish severe and cerebral malaria from moderate and non-cerebral cases. Using a Regularized Random Forest model, we identified 28-gene and 32-gene signatures that can reliably distinguish severe and cerebral malaria, respectively. We tested the specificity of both signatures against other common infectious diseases to ensure the signatures reliability and suitability as diagnostic markers. The severe and cerebral malaria gene-signatures were further integrated through k-top scoring pairs classifiers into ten and nine gene pairs that could distinguish severe and cerebral malaria, respectively. These signatures have various implications that can be utilized as blood diagnostic tools for malaria severity in endemic countries.

Australian mosquito assemblages vary between ground and sub-canopy habitats

Background The surveillance and control of mosquito-borne diseases is dependent upon understanding the bionomics and distribution of the vectors. Most studies of mosquito assemblages describe species abundance, richness and composition close to the ground defined often by only one sampling method. In this study, we assessed Australian mosquito species near the ground and in the sub-canopy using two traps baited with a variety of lures. Methods Mosquitoes were sampled using a 4 × 4 Latin square design at the Cattana Wetlands, Australia from February to April 2020, using passive box traps with octenol and carbon dioxide and three variations of a sticky net trap (unbaited, and baited with octenol or octenol and carbon dioxide). The traps were deployed at two different heights: ground level (≤ 1 m above the ground) and sub-canopy level (6 m above the ground). Results In total, 27 mosquito species were identified across the ground and sub-canopy levels from the different traps. The abundance of mosquitoes at the ground level was twofold greater than at the sub-canopy level. While the species richness at ground and sub-canopy levels was not significantly different, species abundance varied by the collection height. Conclusions The composition of mosquito population assemblages was correlated with the trap types and heights at which they were deployed. Coquillettidia species, which prefer feeding on birds, were mainly found in the sub-canopy whereas Anopheles farauti, Aedes vigilax and Mansonia uniformis, which have a preference for feeding on large mammals, were predominantly found near the ground. In addition to trap height, environmental factors and mosquito bionomic characteristics (e.g. larval habitat, resting behaviour and host blood preferences) may explain the vertical distribution of mosquitoes. This information is useful to better understand how vectors may acquire and transmit pathogens to hosts living at different heights. Graphical abstract

The invasive pathogen Yersinia pestis disrupts host blood vasculature to spread and provoke hemorrhages

Yersinia pestis is a powerful pathogen with a rare invasive capacity. After a flea bite, the plague bacillus can reach the bloodstream in a matter of days giving way to invade the whole organism reaching all organs and provoking disseminated hemorrhages. However, the mechanisms used by this bacterium to cross and disrupt the endothelial vascular barrier remain poorly understood. In this study, an innovative model of in vivo infection was used to focus on the interaction between Y. pestis and its host vascular system. In the draining lymph nodes and in secondary organs, bacteria provoked the porosity and disruption of blood vessels. An in vitro model of endothelial barrier showed a role in this phenotype for the pYV/pCD1 plasmid that carries a Type Three Secretion System. This work supports that the pYV/pCD1 plasmid is responsible for the powerful tissue invasiveness capacity of the plague bacillus and the hemorrhagic features of plague.

Bacterial Microbiota Analysis Demonstrates That Tick Can Acquire Bacteria From Habitat and Host Blood Meal

Exploring the bacterial microbiota is imperative to tick control since it has an important role in tick physiology and vector capacity. The life cycle of ticks consists of parasitic and non-parasitic stages, with a diversity of habitats and host blood meals. Whether and how these factors, such as tick developmental stages, tick organs, habitats and host blood meals affect tick bacterial microbiota is poorly elucidated. In the present study, we investigated the bacterial microbiotas of hard tick Haemaphysalis longicornis, their blood meals and habitats using 16S rRNA high-throughput sequencing. The bacterial richness and diversity in ticks varied depending on the tick developmental stage, feeding status and the tick organs. Results showed that fed ticks present a higher bacterial richness suggesting that ticks may acquire bacteria from blood meals. The significant overlap of the bacteriota of fed ticks and the host blood also support this possibility. Another possibility is that blood meals can stimulate the proliferation of certain bacteria. However, most shared bacteria cannot transmit throughout the tick life cycle, as they were not present in tick eggs. The most shared bacteria between ticks and habitats are genus of Staphylococcus, Pseudomonus, Enterobacter, Acinetobacer and Stenotrophomonas, some of them are also present in tick organ, suggesting that these environmental bacteria cannot be completely washed away and can be acquired by ticks. As tick reproductive organ, ovary showed the lowest bacterial richness and diversity compared to other organs. The predominant proportion of Coxiella in fed females and ovary further demonstrated that this genus is required for H. longicornis reproduction system. These findings further reveal that the bacterial composition of ticks is influenced by a variety of factors and will help in subsequent studies of the function of these bacteria.

Identification of tick-borne pathogens using metagenomic analyses in H. longicornis feeding on humans in downtown Beijing

On August 14th, 2018, a Beijing resident living in Xicheng District found a female H. longicornis tick attached to the skin at the front of his upper shin. On examination, the patient was afebrile and appeared well. The species of the tick was identified through morphological characteristics and phylogenetic analysis based on cytochrome C oxidase subunit I. This H. longicornis tick was screened for tick-borne pathogens such as viruses, bacteria and parasites. RNA pathogens were screened by PCR and sequencing, while DNA pathogens were screened by metagenomic analyses. It was found that the tick was positive for the DNA sequences of zoonotic and animal pathogens such as A. phagocytophilum, Ehrlichia minasensis and C. burnetii. Considering the good health condition of the patient, we hypothesized that the pathogens originated from the tick specimen itself rather than host blood meal. For the first time, our study reveals the possible risk of transmission of tick-borne pathogens to human beings through tick bit in downtown Beijing. Further research is needed to screen for tick-borne pathogens among unfed ticks collected from central Beijing.

Prospective validation of host transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR

We tested performance of host-blood transcriptomic tuberculosis (TB) signatures for active case-finding. Among 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2,923 and 861 were enrolled from five South African communities. Eight signatures were measured by microfluidic RT-qPCR and participants were microbiologically-investigated for pulmonary TB at baseline, and actively surveilled for incident disease through 15 months. Diagnostic AUCs for 61 HIV-uninfected (weighted-prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) prevalent TB cases for the 8 signatures were 0.63-0.79 and 0.65-0.88, respectively. Thereafter, 24 HIV-uninfected and 9 HIV-infected participants progressed to incident TB (1.1 and 1.0 per 100 person-years, respectively). Prognostic AUCs through 15-months follow-up were 0.49-0.66 and 0.54-0.81, respectively. Prognostic performance for incident TB occurring within 6-12 months in HIV-negative participants was higher for all signatures. None of the signatures met WHO Target Product Profile criteria for a triage test to diagnose asymptomatic TB; most signatures met the criteria for symptomatic TB. Prognostic accuracy of most signatures for incident TB within six months of testing met the criteria for an incipient TB test.

Host blood meal identity modifies vector gene expression and competency

A vector’s susceptibility and ability to transmit a pathogen— termed vector competency—determines disease outcomes, yet the ecological factors influencing tick vector competency remain largely unknown. Ixodes pacificus, the tick vector of Borrelia burgdorferi (Bb) in the western U.S., feeds on rodents, birds, and lizards. Unlike rodents and birds which are reservoirs for Bb and infect juvenile ticks, lizards are refractory to Bb and cannot infect feeding ticks. Additionally, the lizard bloodmeal contains borreliacidal properties, clearing previously infected feeding ticks of their Bb infection. Despite I. pacificus feeding on a range of hosts, it is undetermined how the host identity of the larval bloodmeal affects future nymphal vector competency. We experimentally evaluate the influence of larval host bloodmeal on Bb acquisition by nymphal I. pacificus. Larval I. pacificus were fed on either lizards or mice and after molting, nymphs were fed on Bb-infected mice. We found that lizard-fed larvae were significantly more likely to become infected with Bb during their next bloodmeal than mouse-fed larvae. We also conducted the first RNA-seq analysis on whole-bodied I. pacificus and found significant upregulation of tick antioxidants and antimicrobial peptides in the lizard-fed group. Our results indicate that the lizard bloodmeal significantly alters vector competency and gene regulation in ticks, highlighting the importance of host bloodmeal identity in vector-borne disease transmission and upends prior notions about the role of lizards in Lyme disease community ecology.