Rodent-borne parasites in Qatar: A possible risk at the human-animal-ecosystem interface.

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 < 0.05). The sequence analysis of Hymenolepis spp. was closely related to the previously reported H. diminuta in Iran, China, and Mexico. In conclusion, the study identified a diverse range of rodent-borne parasites that are important to public health, with most of them being recorded for the first time among commensal rodents in Qatar.

Immune Mediators Important for a Protective Secondary Response to Babesia microti.

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.

Soil Properties Correlate with Microbial Community Structure in Qatari Arid Soils.

This is the first detailed characterization of the microbiota and chemistry of different arid habitats from the State of Qatar. Analysis of bacterial 16S rRNA gene sequences showed that in aggregate, the dominant microbial phyla were Actinobacteria (32.3%), Proteobacteria (24.8%), Firmicutes (20.7%), Bacteroidetes (6.3%), and Chloroflexi (3.6%), though individual soils varied widely in the relative abundances of these and other phyla. Alpha diversity measured using feature richness (operational taxonomic units [OTUs]), Shannon's entropy, and Faith's phylogenetic diversity (PD) varied significantly between habitats (P = 0.016, P = 0.016, and P = 0.015, respectively). Sand, clay, and silt were significantly correlated with microbial diversity. Highly significant negative correlations were also seen at the class level between both classes Actinobacteria and Thermoleophilia (phylum Actinobacteria) and total sodium (R = -0.82 and P = 0.001 and R = -0.86, P = 0.000, respectively) and slowly available sodium (R = -0.81 and P = 0.001 and R = -0.8 and P = 0.002, respectively). Additionally, class Actinobacteria also showed significant negative correlation with sodium/calcium ratio (R = -0.81 and P = 0.001). More work is needed to understand if there is a causal relationship between these soil chemical parameters and the relative abundances of these bacteria. IMPORTANCE Soil microbes perform a multitude of essential biological functions, including organic matter decomposition, nutrient cycling, and soil structure preservation. Qatar is one of the most hostile and fragile arid environments on earth and is expected to face a disproportionate impact of climate change in the coming years. Thus, it is critical to establish a baseline understanding of microbial community composition and to assess how soil edaphic factors correlate with microbial community composition in this region. Although some previous studies have quantified culturable microbes in specific Qatari habitats, this approach has serious limitations, as in environmental samples, approximately only 0.5% of cells are culturable. Hence, this method vastly underestimates natural diversity within these habitats. Our study is the first to systematically characterize the chemistry and total microbiota associated with different habitats present in the State of Qatar.

Prevalence and microbiological and genetic characteristics of multidrug-resistant Pseudomonas aeruginosa over three years in Qatar.

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.

Incidence of HPVs, EBV, and MMTV-Like Virus in Breast Cancer in Qatar.

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 sample cohorts; 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.

IFN-induced cell-autonomous immune mechanisms in the control of intracellular protozoa.

Vertebrate cells have evolved an elaborate multi-tiered intracellular surveillance system linked to downstream antimicrobial effectors to defend themselves from pathogens. This cellular self-defense system is referred to as cell-autonomous immunity. A wide array of cell-autonomous mechanisms operates to control intracellular pathogens including protozoa such as Toxoplasma gondii. Cell-autonomous immunity consists of antimicrobial defenses that are constitutively active in cells and those that are inducible typically in response to host cell activation. The IFN family of cytokines is an important stimulator of inducible cell-autonomous immunity. There are several hundred interferon-stimulated genes (ISGs); many of them have known roles in inducible cell-autonomous immune mechanisms. The importance of IFN-γ activation of cell-autonomous immunity is evidenced by the fact that many intracellular pathogens have evolved a diversity of molecular mechanisms to inhibit activation of infected cells through the JAK-STAT pathway in response to IFN-γ. The goal of this review is to provide a broad framework for understanding the elaborate system of cell-autonomous immunity that acts as a first line of defense between a host and intracellular parasites.

Genetic diversity of Plasmodium falciparum AMA-1 antigen from the Northeast Indian state of Tripura and comparison with global sequences: implications for vaccine development.

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.

Association of blaVIM-2, blaPDC-35, blaOXA-10, blaOXA-488 and blaVEB-9 ß-Lactamase Genes with Resistance to Ceftazidime-Avibactam and Ceftolozane-Tazobactam in Multidrug-Resistant Pseudomonas aeruginosa.

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 ß-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 ß-lactamase genes, with blaOXA-488 (19%) and blaVEB-9 (45.2%) being predominant. A strong association was detected between class B ß-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 ß-lactamases (blaVIM-2) and class D ß-lactamases (blaOXA-10), while ceftolozane-tazobactam resistance was associated with class A (blaVEB-9), class C (blaVPDC-35), and class D ß-lactamases (blaOXA-488).

Diversity of bacterial pathogens and their antimicrobial resistance profile among commensal rodents in Qatar.

Rodents are sources of many zoonotic pathogens that are of public health concern. This study investigated bacterial pathogens and assessed their antimicrobial resistance (AMR) patterns in commensal rodents in Qatar. A total of 148 rodents were captured between August 2019 and February 2020, and blood, ectoparasites, and visceral samples were collected. Gram-negative bacteria were isolated from the intestines, and blood plasma samples were used to detect antibodies against Brucella spp., Chlamydophila abortus, and Coxiella burnetii. PCR assays were performed to detect C. burnetii, Leptospira spp., Rickettsia spp., and Yersinia pestis in rodent tissues and ectoparasite samples. Antimicrobial resistance by the isolated intestinal bacteria was performed using an automated VITEK analyzer. A total of 13 bacterial species were isolated from the intestine samples, namely Acinetobacter baumannii, Aeromonas salmonicida, Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Hafnia alvei, Klebsiella pneumoniae, Providencia stuartii, Proteus mirabilis, Pseudomonas aeruginosa, and Salmonella enterica. The majority of them were E. coli (54.63%), followed by P. mirabilis (17.59%) and K. pneumoniae (8.33%). Most of the pathogens were isolated from rodents obtained from livestock farms (50.46%), followed by agricultural farms (26.61%) and other sources (22.94%). No antibodies (0/148) were detected against Brucella spp., C. abortus, or C. burnetii. In addition, 31.58% (6/19) of the flea pools and one (1/1) mite pool was positive for Rickettsia spp., and no sample was positive for C. burnetii, Leptospira spp., and Y. pestis by PCR. A total of 43 (38%) bacterial isolates were identified as multidrug resistant (MDR), whereas A. salmonicida (n = 1) did not show resistance to any tested antimicrobials. Over 50% of bacterial MDR isolates were resistant to ampicillin, cefalotin, doxycycline, nitrofurantoin, and tetracycline. The presence of MDR pathogens was not correlated with rodent species or the location of rodent trapping. Seven (11.86%) E. coli and 2 (22.2%) K. pneumoniae were extended-spectrum beta-lactamases (ESBL) producers. These findings suggest that rodents can be a source of opportunistic bacteria for human and animal transmission in Qatar. Further studies are needed for the molecular characterization of the identified bacteria in this study.

Assessing the impact of climate conditions on the distribution of mosquito species in Qatar.

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.

Clinical outcomes, molecular epidemiology and resistance mechanisms of multidrug-resistant Pseudomonas aeruginosa isolated from bloodstream infections from Qatar.

BACKGROUND: 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 ß-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 <5% of P. aeruginosa blood isolates over three years.Typical risk factors for MDR infections were highly prevalent in the study population and overall clinical outcomes are consistent with those previously reported.Colistin was the only agent with consistent antibacterial activity against the study isolates.

Identification and characterisation of mosquitoes from different locations in Qatar in 2017-2019.

Mosquito-borne infections have considerable consequences for public health. The mere presence of a single case of vector-borne disease (VBD) introduces a risk to the local community particularly when associated with the compatible vector, host, and suitable environmental factors. Presently, there is no well-established vector control and surveillance programme in Qatar; therefore, the likelihood of VBDs spreading is undetermined. As a result, there is a pressing need to address this gap and enable successful management of VBDs. This study presents the results of three consecutive field surveys conducted between 2017 and 2019 with the aim of defining the types and distribution of mosquitoes that are of public health importance in Qatar. The results of the adult mosquito trappings show that the southern house mosquito Culex quinquefasciatus is the most widespread and abundant mosquito species, followed by Cx. perexiguus, both species representing a risk of West Nile virus transmission. All sampling methods show that the malaria vector Anopheles stephensi is widespread including in urbanised areas, suggesting a risk of local malaria transmission. The wetland mosquito Aedes caspius is also widespread, representing a risk of Rift Valley fever virus transmission. The dengue vector Ae. aegypti was not detected and can be considered neither widespread nor abundant, suggesting a minimal risk for local transmission of dengue, chikungunya and Zika viruses. Interestingly, the study detected Culiseta longiareolata for the first time in Qatar. Regular field studies are needed to further address the knowledge gaps in terms of distribution, ecology, and biting habits of different mosquito species currently present in Qatar to accurately assess the risk of mosquito-borne diseases.

TITLE: Identification et caractérisation des moustiques de différents sites du Qatar en 2017­2019. ABSTRACT: Les maladies transmises par les moustiques posent de considérables risques en santé publique. La simple présence d'un cas de maladie à transmission vectorielle (MTV) introduit un risque pour la communauté locale lorsque associé à un vecteur, un hôte et des facteurs environnementaux compatibles. À ce jour il n'y a pas de programme de surveillance et de contrôle des vecteurs bien établi au Qatar, et de ce fait la probabilité de diffusion de MTV est indéterminée. C'est pourquoi il existe un besoin pressant de combler ce vide et de permettre une gestion effective des MTV. Ce travail présente les résultats de trois études de terrain successives conduites entre 2017 et 2019, dans l'objectif de caractériser les moustiques d'importance en santé publique et leur distribution au Qatar. Les résultats des piégeages d'adultes révèlent que le moustique domestique méridional Culex quinquefasciatus est l'espèce la plus répandue et abondante, suivie de Cx. perexiguus, les deux espèces présentant un risque pour la transmission du virus West Nile. L'ensemble des échantillonnages montrent que le vecteur du paludisme Anopheles stephensi est largement répandu y compris dans les zones urbanisées, ce qui suggère un risque de transmission locale du paludisme. Le moustique des zones humides Aedes caspius est également largement répandu, présentant un risque pour la transmission du virus de la fièvre de la Vallée du Rift. Le vecteur de la dengue Ae. aegypti n'a pas été détecté et peut être considéré ni répandu ni abondant, ce qui suggère un risque minimal de transmission locale des virus dengue, chikungunya et Zika. Il est intéressant de noter que cette étude a détecté la présence de Culiseta longiareolata pour la première fois au Qatar. Des études de terrain régulières sont nécessaires pour mieux combler les lacunes de connaissances en termes de distribution, écologie et comportement trophique des différentes espèces de moustiques présentes au Qatar, et d'évaluer plus précisément le risque de maladies transmises par les moustiques.

Epidemiology of Multidrug-Resistant Pseudomonas aeruginosa in the Middle East and North Africa Region.

Over the last decades, there has been a dramatic global increase in multidrug-resistant (MDR) pathogens particularly among Gram-negative bacteria (GNB). Pseudomonas aeruginosa is responsible for various health care-associated infections, while MDR P. aeruginosa causes significant morbidity and mortality. Middle East and North Africa (MENA) represent an unexplored geographical region for the study of drug resistance since many of these countries are at crossroads of high volume of travel, diverse expatriate populations, as well as high antibiotic consumption despite attempts to implement antimicrobial stewardship programs. This minireview analyzes epidemiology, microbiological, and genomic characteristics of MDR P. aeruginosa in the MENA region. Published data on MDR P. aeruginosa prevalence, antimicrobial resistance patterns, and genetic profiles from studies published during the past 10 years from 19 MENA countries have been included in this minireview. There is wide variation in the epidemiology of MDR P. aeruginosa in the MENA region in terms of prevalence, antimicrobial characteristics, as well as genetic profiles. Overall, there is high prevalence of MDR P. aeruginosa seen in the majority of the countries in the MENA region with similarities between neighboring countries, which might reflect comparable population and antibiotic-prescribing cultures. Isolates from critical care units are significantly resistant particularly from certain countries such as Saudi Arabia, Egypt, Libya, Syria, and Lebanon with high-level resistance to cephalosporins, carbapenems, and aminoglycosides. Colistin susceptibility patterns remains high apart from countries with high-level antibiotic resistance such as Saudi Arabia, Syria, and Egypt.

A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic.

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.

The co-presence of high-risk human papillomaviruses and Epstein-Barr virus is linked with tumor grade and stage in Qatari women with breast cancer.

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.

A Review of the Progress and Challenges of Developing a Vaccine for COVID-19.

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.

ß-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar.

BACKGROUND: The distribution of ß-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 ß-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 ß-lactamases (n = 72, 96% each), while metallo-ß-lactamases were detected in 20 (26.7%) isolates. Eight (40%) metallo-ß-lactamase producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum ß-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 ß-lactams. CONCLUSION: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal ß-lactams. High-risk STs are predominant in Qatar and their associated MDR phenotypes are a cause for considerable concern.

Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman.

Mixed species infections of Theileria spp. are common in nature. Experimental and epidemiological data suggest that mixed species infections elicit cross-immunity that can modulate pathogenicity and disease burden at the population level. The present study examined within-host interactions, over a period of 13 months during natural infections with two Theileria spp., pathogenic (T. lestoquardi) and non-pathogenic (T. ovis), amongst a cohort of naive sheep in Oman. In the first two months after exposure to infection, a high rate of mortality was seen among sheep infected with T. lestoquardi alone. However, subsequently mixed-infections of T. lestoquardi and T. ovis prevailed, and no further death occurred. The overall densities of both parasite species were significantly higher as single infection vs mixed infection and the higher relative density of pathogenic T. lestoquardi indicated a competitive advantage over T. ovis in mixed infection. The density of both species fluctuated significantly over time, with no difference in density between the very hot (May to August) and warm season (September to April). A high degree of genotype multiplicity was seen among T. lestoquardi infections, which increased with rising parasite density. Our results illustrate a potential competitive interaction between the two ovine Theileria spp., and a substantial reduction in the risk of mortality in mixed parasite infections, indicating that T. ovis confers heterologous protection against lethal T. lestoquardi infection.

Distribution pattern of amino acid mutations in chloroquine and antifolate drug resistance associated genes in complicated and uncomplicated Plasmodium vivax isolates from Chandigarh, North India.

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 (M958/L1076) was found in 99% of the clinical isolates. Among the pyrimethamine resistance-associated gene Pvdhfr, the double mutant haplotype I13P33F57R58T61N117I173 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.