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Biocrusts dominate the soil surface in deserts and are composed of diverse microbial communities that provide important ecosystem services. Cyanobacteria in biocrusts produce many secondary metabolites, including the neurotoxins BMAA, AEG, DAB, anatoxin-a(S) (guanitoxin), and the microcystin hepatotoxins, all known or suspected to cause disease or illness in humans and other animals. We examined cyanobacterial growth and prevalence of these toxins in biocrusts at millimeter-scales, under a desert-relevant illumination gradient. In contrast to previous work, we showed that hydration had an overall positive effect on growth and toxin accumulation, that nitrogen was not correlated with growth or toxin production, and that phosphorus enrichment negatively affected AEG and BMAA concentrations. Excess illumination positively correlated with AEG, and negatively correlated with all other toxins and growth. Basic pH negatively affected only the accumulation of BMAA. Anatoxin-a(S) (guanitoxin) was not correlated with any tested variables, while microcystins were not detected in any of the samples. Concerning toxin pools, AEG and BMAA were good predictors of the presence of one another. In a newly conceptualized scheme, we integrate aspects of biocrust growth and toxin pool accumulations with arid-relevant desertification drivers.

Rodents are known reservoirs for a diverse group of zoonotic pathogens that can pose a threat to human health. Therefore, it is crucial to investigate these pathogens to institute prevention and control measures. To achieve this, the current study was conducted to investigate the frequency of different parasites in commensal rodents in Qatar. A total of 148 rodents, including Rattus norvegicus, Rattus rattus, and Mus musculus were captured using traps placed in different habitats such as agricultural and livestock farms, residential areas, and other localities. Blood, feces, ectoparasite, and visceral organs were collected for gross, microscopic, immunological, and molecular analysis. The study identified 10 different parasites, including Capillaria annulosa, Eimeria spp., Giardia spp., Hymenolepis diminuta, Mastophorus muris, Ornithonyssus bacoti, Taenia taeniaeformis, Toxoplasma gondii, Trypanosoma lewisi, and Xenopsylla astia. Overall, 62.2% of the rodents tested positive for at least one parasite species. Helminths were found to be the most prevalent parasites (46.0%), followed by ectoparasites (31.8%), and protozoa (10.1%). However, individually, X. astia was the most prevalent (31.8%), whereas C. annulosa was the least common (0.7%). The prevalence of X. astia and H. diminuta significantly differed between habitats (p

Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti.

IntroductionAmong Gram-negative bacteria (GNB), Enterobacterales (Enterobacterales), such as Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), are the most clinically relevant pathogens in healthcare settings. Infections secondary to these pathogens are widely common but multidrug resistance (MDR) in Enterobacterales has become a significant challenge with increased morbidity, mortality, and cost of management. The escalating global prevalence of MDR in Enterobacterales has led to limited treatment options, raising an urgent need for novel antimicrobial therapy(s) and detailed studies exploring underlying resistance mechanisms. In Enterobacterales, the prime antimicrobial resistance mechanism against β-lactam antibiotics is mainly the production of β-lactamases, particularly extended-spectrum β-lactamases (ESBLs). Although the Gulf region is witnessing major challenges from infections secondary to MDR GNB, the extent of the problem has not been fully evaluated. Therefore, this review aims to address the prevalence and genetic characterization of ESBL-producing Enterobacterales in the Gulf Cooperation Council (GCC) countries.MethodsPubMed® (National Library of Medicine, Bethesda, MD, USA) search was conducted, which looked for academic articles discussing the epidemiology of MDR Enterobacterales in the GCC countries, published in the last 5 years.Results and conclusionsIn GCC countries there is a high prevalence rate of MDR Enterobacterales, particularly ESBLs. Prevalence rates of ESBL-producing Enterobacterales among the Enterobacterales in general clinical samples in the GCC region is 21.6%–29.3%, with a slightly higher prevalence rate in intensive care unit patients (17.3–31.3%) and in patients with urinary tract infections (25.2%–31.7%). ESBL carriers have also been noted in the general community. ESBL-producing Enterobacterales from the GCC region show high levels of resistance to ampicillin, aztreonam, third-/fourth-generation cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole. Intermediate resistance rates are observed against nitrofurantoin, piperacillin/tazobactam, and gentamicin, with increasing resistance observed against tigecycline. The isolates demonstrate low-level resistance to carbapenems, fosfomycin, colistin, and amikacin. Enterobacterales isolates that are concomitant ESBL producers and are carbapenem resistant have been increasingly reported and demonstrate alarmingly increased antibiotic resistance patterns compared with ESBL Enterobacterales. The most prevalent genes for ESBL resistance in the Enterobacterales isolates in the GCC region are: blaCTX-M (subtype group 1) followed by/co-dominated by blaTEM and blaSHV, whereas the most common carbapenem-resistant genes are blaOXA-48 and blaNDM-1.

Abstract Background Malaria continues to be a major public health problem in the Northeastern part of India despite the implementation of vector control measures and changes in drug policies. To develop successful vaccines against malaria, it is important to assess the diversity of vaccine candidate antigens in field isolates. This study was done to assess the diversity of Plasmodium falciparum AMA-1 vaccine candidate antigen in a malaria-endemic region of Tripura in Northeast India and compare it with previously reported global isolates with a view to assess the feasibility of developing a universal vaccine based on this antigen. Methods Patients with fever and malaria-like illness were screened for malaria and P. falciparum positive cases were recruited for the current study. The diversity of PfAMA-1 vaccine candidate antigen was evaluated by nested PCR and RFLP. A selected number of samples were sequenced using the Sanger technique. Results Among 56 P. falciparum positive isolates, Pfama-1 was successfully amplified in 75% (n = 42) isolates. Allele frequencies of PfAMA-1 antigen were 16.6% (n = 7) for 3D7 allele and 33.3% (n = 14) in both K1 and HB3 alleles. DNA sequencing revealed 13 haplotypes in the Pfama-1 gene including three unique haplotypes not reported earlier. No unique amino-acid substitutions were found. Global analysis with 2761 sequences revealed 435 haplotypes with a very complex network composition and few clusters. Nucleotide diversity for Tripura (0.02582 ± 0.00160) showed concordance with South-East Asian isolates while recombination parameter (Rm = 8) was lower than previous reports from India. Population genetic structure showed moderate differentiation. Conclusions Besides documenting all previously reported allelic forms of the vaccine candidate PfAMA-1 antigen of P. falciparum, new haplotypes not reported earlier, were found in Tripura. Neutrality tests indicate that the Pfama-1 population in Tripura is under balancing selection. This is consistent with global patterns. However, the high haplotype diversity observed in the global Pfama-1 network analysis indicates that designing a universal vaccine based on this antigen may be difficult. This information adds to the existing database of genetic diversity of field isolates of P. falciparum and may be helpful in the development of more effective vaccines against the parasite.

Qatar is a peninsular country with predominantly hot and humid weather, with 88% of the total population being immigrants. As such, it leaves the country liable to the introduction and dissemination of vector-borne diseases, in part due to the presence of native arthropod vectors. Qatar's weather is expected to become warmer with the changing climatic conditions across the globe. Environmental factors such as humidity and temperature contribute to the breeding and distribution of different types of mosquito species in a given region. If proper and timely precautions are not taken, a high rate of particular mosquito species can result in the transmission of various vector-borne diseases. In this study, we analyzed the environmental impact on the probability of occurrence of different mosquito species collected from several different sites in Qatar. The Naive Bayes model was used to calculate the posterior probability for various mosquito species. Further, the resulting Naive Bayes predictions were used to define the favorable environmental circumstances for identified mosquito species. The findings of this study will help in the planning and implementation of an active surveillance system and preventive measures to curb the spread of mosquitoes in Qatar.

High-risk human papillomaviruses (HPV) can be present and cooperate with Epstein–Barr virus (EBV) to promote the onset and/or progression of various cancers including cervical, breast, head and neck as well as colorectal. In this investigation, we explored the co-prevalence of high-risk HPV and EBV in 74 breast cancer tissues from Qatari women using polymerase chain reaction. We found that high-risk HPV and EBV are present in 48/74 (65%) and 36/74 (49%) of the cases, respectively. While we noted that the presence of HPV presence is associated with triple-negative breast cancer (TNBC) (p = .008), however, the presence of EBV did not correlate with any breast cancer subgroup. Moreover, our data revealed that high-risk HPV and EBV are co-present in 35/74 (47%) of the samples and their co-presence is significantly associated with tumor grade (p = .04) and tumor stage (p = .04). These data indicate that HPV and EBV are commonly co-present in breast cancer and their association could be linked with a more aggressive tumor phenotype. Thus, further investigations are essential to understand the underlying mechanisms of HPV and EBV cooperation in breast carcinogenesis.

AbstractBackground Bloodstream infections (BSIs) caused by multidrug-resistant (MDR)-Pseudomonas aeruginosa are associated with poor clinical outcomes, at least partly due to delayed appropriate antimicrobial therapy. The characteristics of MDR-P. aeruginosa bloodstream isolates have not been evaluated in Qatar. Our study aimed to examine in vitro susceptibility, clinical and molecular characteristics, and mechanisms of resistance of MDR-P. aeruginosa bloodstream isolates from Qatar.Materials and methods We included all MDR-P. aeruginosa isolated from blood cultures taken between October 2014 and September 2017. Blood cultures were processed using BD BACTEC™ FX automated system. BD Phoenix™ was used for identification, Liofilchem® MIC Test Strips for MIC determination. Whole-genome sequencing was performed using the Illumina-HiSeq-2000.Results Out of 362 P. aeruginosa bloodstream isolates, 16 (4.4%) were MDR. The median patient age was 55 years (range 43–81) and all patients presented with septic shock. Most patients received meropenem (12/16) and/or colistin (10/16). Clinical response was achieved in eight patients, and five patients died within 30-days. MDR-P. aeruginosa isolates belonged to 13 different sequence types. All isolates were non-susceptible to cefepime and ciprofloxacin. The most active agents were colistin (16/16) and aztreonam (10/16). Seven isolates produced blaVIM, and four possessed genes encoding extended-spectrum β-lactamases. Aminoglycoside modifying enzymes were present in 15/16, transferable qnr-mediated quinolone resistance gene was detected in 3/16, and the novel ciprofloxacin modifying enzyme CrpP-encoding gene in one isolate.Conclusion MDR-P. aeruginosa BSIs are relatively uncommon in Qatar but are highly resistant, harbour multiple resistance genes, and are commonly associated with unfavourable clinical outcomes. Colistin was the only agent with consistent activity against the study isolates.Key messagesMDR-P. aeruginosa constituted

Introduction: Human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus-like virus (MMTV-like virus) can be present and contribute to breast cancer development and progression. However, the role of these oncoviruses and their crosstalk in breast cancer is still unclear. Methods: We explored the co-presence of high-risk HPVs, EBV, and MMTV-like virus in 74 breast cancer samples from Qatar using PCR. Results: We found the presence of HPV and EBV in 65% and 49% of our cancer samples cohort; 47% of the samples are positive for both oncoviruses. The MMTV-like virus alone was detected in 15% of the samples with no significant association with clinicopathological features. The three oncoviruses were co-present in 14% of the cases; No significant association was noted between the co-presence of these viruses and the clinicopathological features. Conclusion: Despite the presence of the oncoviruses, additional studies are necessary to understand their interactions in human breast carcinogenesis.

Abstract Background The distribution of β-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. We used whole-genome sequencing (WGS) to identify the predominant sequence types (ST) and β-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from Qatar Methods Microbiological identification and susceptibility tests were performed by automated BD Phoenix™ system and manual Liofilchem MIC Test Strips. Results Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n = 36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n = 21, 28%) and aztreonam (n = 16, 21.3%). All isolates possessed Class C and/or Class D β-lactamases (n = 72, 96% each), while metallo-β-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-β-lactamase producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum β-lactamases. High risk ST235 (n = 16, 21.3%), ST357 (n = 8, 10.7%), ST389 and ST1284 (6, 8% each) were most frequent. Nearly all ST235 isolates (15/16; 93.8%) were resistant to all tested β-lactams. Conclusion MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal β-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.

Abstract Background The increasing antimalarial drug resistance is a significant hindrance to malaria control and elimination programs. For the last six decades, chloroquine (CQ) plus pyrimethamine remains the first-line treatment for P. vivax malaria. Regions where both P. falciparum and P. vivax co-exist, P. vivax is exposed to antifolate drugs due to either misdiagnosis or improper treatment that causes selective drug pressure to evolve. Therefore, the present study aims to estimate antimalarial drug resistance among the complicated and uncomplicated P. vivax patients. Methods A total of 143 P. vivax malaria positive patients were enrolled in this study, and DNA was isolated from their blood samples. Pvcrt-o, Pvmdr-1, Pvdhps, and Pvdhfr genes were PCRs amplified, and drug resistance-associated gene mutations were analyzed. Statistical analysis of the drug resistance genes and population diversity was performed using MEGA vs. 7.0.21 and DnaSP v software. Results Among the CQ resistance marker gene Pvcrt-o, the prevalence of K10 insertion was 17.5% (7/40) and 9.5% (7/73) of complicated and uncomplicated P vivax group isolates respectively. In Pvmdr-1, double mutant haplotype (M 958 /L 1076 ) was found in 99% of the clinical isolates. Among the pyrimethamine resistance-associated gene Pvdhfr, the double mutant haplotype I13P33F57 R 58 T61 N 117 I173 was detected in 23% (11/48) in complicated and 20% (17/85) in uncomplicated group isolates. In the sulphadoxine resistance-associated Pvdhps gene, limited polymorphism was observed with the presence of a single mutant (D459A) among 16 and 5% of the clinical isolates in the complicated and uncomplicated group respectively. Conclusion The study presents the situations of polymorphism in the antimalarial drug resistance-associated genes and emphasizes the need for regular surveillance. It is imperative for the development of suitable antimalarial drug policy in India.

Abstract Background In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies. Methods We designed and synthetized a peptide that corresponds to the full sequence of the surface-exposed FG loop. We tested the antigenicity of the linear and the cyclic peptides against HPV16 L1 monoclonal antibodies. We used ELISA to detect anti-peptide antibodies in sera and cervical secretions of 179 Tunisian women, and we applied polymerase chain reaction and direct sequencing methods to detect and genotype HPV DNA. Results Both the linear and the cyclic peptides were recognized by the same neutralizing monoclonal antibodies, but the cyclic peptide was more reactive with human sera. The prevalence of the anti-peptide antibodies in sera was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (44% and 15%, respectively). This contrasts with HPV16 DNA prevalence. Compared to women from the general population, systemic IgG prevalence was significantly higher among sex workers (25%; P = 0.002) and women with LGSIL (44%; P = 0.001). In addition, systemic IgA and cervical IgG prevalence was higher among sex workers only (P = 0.002 and P = 0.001, respectively). We did not observe anti-peptide IgG antibodies in women with a current HPV16 infection. Conclusion Anti-peptide IgG in sera or in cervical secretions could be markers of an effective natural immunization against HPV16. This may open novel perspectives for monitoring vaccinated women and for the design of synthetic peptide-based vaccines.

Abstract Background Successful control programs have impeded local malaria transmission in almost all Gulf Cooperation Council (GCC) countries: Qatar, Bahrain, Kuwait, Oman, the United Arab Emirates (UAE) and Saudi Arabia. Nevertheless, a prodigious influx of imported malaria via migrant workers sustains the threat of local transmission. Here we examine the origin of imported malaria in Qatar, assess genetic diversity and the prevalence of drug resistance genes in imported Plasmodium falciparum, and finally, address the potential for the reintroduction of local transmission. Methods This study examined imported malaria cases reported in Qatar, between 2013 and 2016. We focused on P. falciparum infections and estimated both total parasite and gametocyte density, using qPCR and qRT-PCR, respectively. We also examined ten neutral microsatellites and four genes associated with drug resistance, Pfmrp1, Pfcrt, Pfmdr1, and Pfkelch13, to assess the genetic diversity of imported P. falciparum strains, and the potential for propagating drug resistance genotypes respectively. Results The majority of imported malaria cases were P. vivax, while P. falciparum and mixed species infections (P. falciparum / P. vivax) were less frequent. The primary origin of P. vivax infection was the Indian subcontinent, while P. falciparum was mostly presented by African expatriates. Imported P. falciparum strains were highly diverse, carrying multiple genotypes, and infections also presented with early- and late-stage gametocytes. We observed a high prevalence of mutations implicated in drug resistance among these strains, including novel SNPs in Pfkelch13. Conclusions The influx of genetically diverse P. falciparum, with multiple drug resistance markers and a high capacity for gametocyte production, represents a threat for the reestablishment of drug-resistant malaria into GCC countries. This scenario highlights the impact of mass international migration on the reintroduction of malaria to areas with absent or limited local transmission.

Abstract Background Infections by both human oncoviruses, human Papillomaviruses (HPV) and Epstein–Barr virus (EBV) are very common in the adult human population and are associated with various malignancies. While HPV is generally transmitted sexually or via skin-to-skin contact, EBV is frequently transmitted by oral secretions, blood transfusions and organ transplants. This study aims to determine the prevalence and circulating genotypes of HPV and EBV in healthy blood donors in Qatar. Methods We explored the co-prevalence of high-risk HPVs and EBV in 378 males and only 7 females blood donors of different nationalities (mainly from Qatar, Egypt, Syria, Jordan, Pakistan, and India) residing in Qatar, using polymerase chain reaction (PCR). DNA was extracted from the buffy coat and genotyping was performed using PCR and nested-PCR targeting E6 and E7 as well as LMP-1 of HPV and EBV, respectively. Results We found that from the total number of 385 cases of healthy blood donors studied, 54.8% and 61% of the samples are HPVs and EBV positive, respectively. Additionally, our data revealed that the co-presence of both high-risk HPVs and EBV is 40.4% of the total samples. More significantly, this study pointed out for the first time that the most frequent high-risk HPV types in Qatar are 59 (54.8%), 31 (53.7%), 52 (49.1%), 51 (48.6%), 58 (47%) and 35 (45.5%), while the most commonly expressed low-risk HPV types are 53 (50.6%), 11 (45.5), 73 (41.7%) and 6 (41.3%), with all the cases showing multiple HPVs infection. Conclusion In this study, we demonstrated for the first time that HPV and EBV are commonly co-present in healthy blood donors in Qatar. On the other hand, it is important to highlight that these oncoviruses can also be co-present in several types of human cancers where they can cooperate in the initiation and/or progression of these cancers. Therefore, more studies regarding the co-presence of these oncoviruses and their interaction are necessary to understand their cooperative role in human diseases.

Abstract Objectives: Antimicrobial resistance (AMR) is a global priority with significant clinical and economic consequences. Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the major pathogens associated with significant morbidity and mortality. In healthcare settings, the evaluation of prevalence, microbiological characteristics, as well as mechanisms of resistance is of paramount importance to overcome associated challenges. Methods: Consecutive clinical specimens of P. aeruginosa were collected prospectively from 5 acute-care and specialized hospitals between October 2014 and September 2017, including microbiological, clinical characteristics and outcomes. Identification and antimicrobial susceptibility test were performed using the BD Phoenix identification and susceptibility testing system, matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS), and minimum inhibitory concentration (MIC) test strips. Overall, 78 selected MDR P. aeruginosa isolates were processed for whole-genome sequencing (WGS). Results: The overall prevalence of MDR P. aeruginosa isolates was 5.9% (525 of 8,892) and showed a decreasing trend; 95% of cases were hospital acquired and 44.8% were from respiratory samples. MDR P. aeruginosa demonstrated >86% resistance to cefepime, ciprofloxacin, meropenem, and piperacillin-tazobactam but 97.5% susceptibility to colistin. WGS revealed 29 different sequence types: 20.5% ST235, 10.3% ST357, 7.7% ST389, and 7.7% ST1284. ST233 was associated with bloodstream infections and increased 30-day mortality. All ST389 isolates were obtained from patients with cystic fibrosis. Encoded exotoxin genes were detected in 96.2% of isolates. Conclusions: MDR P. aeruginosa isolated from clinical specimens from Qatar has significant resistance to most agents, with a decreasing trend that should be explored further. Genomic analysis revealed the dominance of 5 main clonal clusters associated with mortality and bloodstream infections. Microbiological and genomic monitoring of MDR P. aeruginosa has enhanced our understanding of AMR in Qatar.

Abstract Background Malaria is one of the important vector-borne diseases with high fatality rates in tropical countries. The pattern of emergence and spread of novel antigenic variants, leading to escape of vaccine-induced immunity might be factors responsible for severe malaria. A high level of polymorphism has been reported among malarial antigens which are under selection pressure imposed by host immunity. There are limited reports available on comparative stage-specific genetic diversity among Plasmodium vivax candidate genes in complicated vivax malaria. The present study was planned to study genetic diversity (Pvcsp and Pvs25) among complicated and uncomplicated P. vivax isolates. Methods Pvcsp and Pvs2-specific PCRs and DNA sequencing were performed on P. vivax PCR positive samples. Genetic diversity was analysed using appropriate software. Results The present study was carried out on 143 P. vivax clinical isolates, collected from Postgraduate Institute of Medical Education and Research, Chandigarh. Among the classic and variant types of Pvcsp, the VK210 (99%; 115/116) was found to be predominant in both complicated and uncomplicated group isolates. Out of the various peptide repeat motifs (PRMs) observed, GDRADGQPA (PRM1) and GDRAAGQPA (PRM2) was the most widely distributed among the P. vivax isolates. Whereas among the Pvs25 isolates, 100% of double mutants (E97Q/I130T) in both the complicated (45/45) as well as in the uncomplicated (81/81) group was observed. Conclusion An analysis of genetic variability enables an understanding of the role of genetic variants in severe vivax malaria.

Epstein-Barr virus (EBV) is a well-characterized oncovirus, associated with several malignancies. The complex and heterogeneous nature of colorectal cancer (CRC) has led to many epidemiological causal associations with CRC. However, a direct causal link between microbial infections and CRC has not been established yet. Our review indicates that the current evidence for the presence and role in EBV in CRC is insufficient and contradictory. The design of the analyzed studies, sample size as well as methodology used for EBV detection varied markedly and consequently may not lead to meaningful conclusions. The presence of EBV in other colorectal tumors (lymphomas, smooth muscle tumors) is in line with their status at other anatomic locations and may have therapeutic implications with EBV-specific vaccines. On the other hand, studies exploring EBV in colorectal adenoma-carcinoma sequence and its molecular genetic characteristics are largely missing and may significantly contribute to a better understanding of the role of EBV in CRC.

Over the last decades, there has been a dramatic global increase in multidrug-resistant (MDR) pathogens particularly among Gram-negative bacteria (GNB). Pseudomonas aeruginosaP. aeruginosa

COVID-19 emerged from China in December 2019 and during 2020 spread to every continent including Antarctica. The coronavirus, SARS-CoV-2, has been identified as the causative pathogen, and its spread has stretched the capacities of healthcare systems and negatively affected the global economy. This review provides an update on the virus, including the genome, the risks associated with the emergence of variants, mode of transmission, immune response, COVID-19 in children and the elderly, and advances made to contain, prevent and manage the disease. Although our knowledge of the mechanics of virus transmission and the immune response has been substantially demystified, concerns over reinfection, susceptibility of the elderly and whether asymptomatic children promote transmission remain unanswered. There are also uncertainties about the pathophysiology of COVID-19 and why there are variations in clinical presentations and why some patients suffer from long lasting symptoms—“the long haulers.” To date, there are no significantly effective curative drugs for COVID-19, especially after failure of hydroxychloroquine trials to produce positive results. The RNA polymerase inhibitor, remdesivir, facilitates recovery of severely infected cases but, unlike the anti-inflammatory drug, dexamethasone, does not reduce mortality. However, vaccine development witnessed substantial progress with several being approved in countries around the globe.

A novel coronavirus, which has been designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in December 2019 in Wuhan China and causes the highly infectious disease referred to as COVID-19. COVID-19 has now spread worldwide to become a global pandemic affecting over 24 million people as of August 26th, 2020 and claimed the life of more than 800,000 people worldwide. COVID-19 is asymptomatic for some individuals and for others it can cause symptoms ranging from flu-like to acute respiratory distress syndrome (ARDS), pneumonia and death. Although it is anticipated that an effective vaccine will be available to protect against COVID-19, at present the world is relying on social distancing and hygiene measures and repurposed drugs. There is a worldwide effort to develop an effective vaccine against SARS-CoV-2 and, as of late August 2020, there are 30 vaccines in clinical trials with over 200 in various stages of development. This review will focus on the eight vaccine candidates that entered Phase 1 clinical trials in mid-May, including AstraZeneca/Oxford's AZD1222, Moderna's mRNA-1273 and Sinovac's CoronaVac vaccines, which are currently in advanced stages of vaccine development. In addition to reviewing the different stages of vaccine development, vaccine platforms and vaccine candidates, this review also discusses the biological and immunological basis required of a SARS-CoV-2 vaccine, the importance of a collaborative international effort, the ethical implications of vaccine development, the efficacy needed for an immunogenic vaccine, vaccine coverage, the potential limitations and challenges of vaccine development. Although the demand for a vaccine far surpasses the production capacity, it will be beneficial to have a limited number of vaccines available for the more vulnerable population by the end of 2020 and for the rest of the global population by the end of 2021.

ABSTRACT Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.

Ceftazidime–avibactam and ceftolozane–tazobactam are approved for the treatment of complicated Gram-negative bacterial infections including multidrug-resistant (MDR) Pseudomonas aeruginosa. Resistance to both agents has been reported, but the underlying mechanisms have not been fully explored. This study aimed to correlate β-lactamases with phenotypic resistance to ceftazidime–avibactam and/or ceftolozane–tazobactam in MDR-P. aeruginosa from Qatar. A total of 525 MDR-P. aeruginosa isolates were collected from clinical specimens between 2014 and 2017. Identification and antimicrobial susceptibility were performed by the BD PhoenixTM system and gradient MIC test strips. Of the 75 sequenced MDR isolates, 35 (47%) were considered as having difficult-to-treat resistance, and 42 were resistant to ceftazidime–avibactam (37, 49.3%), and/or ceftolozane–tazobactam (40, 53.3%). They belonged to 12 sequence types, with ST235 being predominant (38%). Most isolates (97.6%) carried one or more β-lactamase genes, with blaOXA-488 (19%) and blaVEB-9 (45.2%) being predominant. A strong association was detected between class B β-lactamase genes and both ceftazidime–avibactam and ceftolozane–tazobactam resistance, while class A genes were associated with ceftolozane–tazobactam resistance. Co-resistance to ceftazidime–avibactam and ceftolozane–tazobactam correlated with the presence of blaVEB-9, blaPDC-35, blaVIM-2, blaOXA-10 and blaOXA-488. MDR-P. aeruginosa isolates resistant to both combination drugs were associated with class B β-lactamases (blaVIM-2) and class D β-lactamases (blaOXA-10), while ceftolozane–tazobactam resistance was associated with class A (blaVEB-9), class C (blaVPDC-35), and class D β-lactamases (blaOXA-488).

Abstract Background In the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the plasma-based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened up an era of identification of early biomarkers for various infectious and non-infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of length 19–24 nts and are responsible for the regulation of the majority of human gene expressions at post transcriptional level. Methods We identified the differentially expressed miRNAs by microarray and validated the selected miRNAs by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to construct protein–protein and mRNA–miRNA networks to identify highly regulated miRNA. Results In the present study, utility of miRNA as potential biomarker of complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR-7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were found to be significantly up-regulated in complicated P. vivax malaria patients using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be significant with sensitivity and specificity of 60–71% and 69–81% respectively and area under curve (AUC) of 0.7 (p

Abstract Background Cervical cancer is the fourth most common cancer in women worldwide with highest incidence reported in Eastern Africa in 2012. The primary goal of this study was to study the expression of p16INK4a in squamous cell carcinoma (SCC) of the cervix by immunohistochemistry (IHC) and determine relation with clinico-pathological parameters. This study further explored the correlation of p16INK4a immunostaining with another proliferation marker, Ki-67 and to study if human papillomavirus (HPV) IHC can be used as a marker for detection of virus in high-grade dysplasia. Methods A total of 90 samples, diagnosed for cervical cancer, were included in the study. Fixed Paraffin Embedded (FFPE) tissue sections were stained with anti-p16INK4a, anti-Ki-67 and anti-HPV antibodies using automated immunohistochemistry platform (ASLink 48-DAKO). Results Immunohistochemical protein expression of p16INK4a positivity was found to be highest in SCC (92.2%, n = 71) than other HPV tumors (76.9%, n = 10). The majority of cases (97.4%) were p16INK4a positive in the age group 41–60 years. In addition, a statistically significant difference between p16INK4a and HPV was observed among total cervical tumor cases and SCC cases. Conclusions As expected staining of invasive cervical cancer with anti-HPV showed rare positivity because HPV heralds active infection in dysplastic lesions and not of frank cervical carcinoma. In contrast, anti-p16INK4a IHC results showed positive correlation in SCC and other cervical tumors.