Reservoir Of Infection Research Articles

Neurological complications of HIV infection

The fact that HIV infection directly impacts the central nervous system (CNS) has been recognized since very early in the global HIV epidemic. The emergence of widespread antiretroviral therapy (ART) use has altered the clinical character of neurologic disease observed in HIV, led to new challenges related to optimization of CNS treatment, and raised a host of questions related to the role of the CNS as a potential barrier to HIV eradication and cure. This presentation will review key issues in this landscape of clinical and scientific issues facing people living with HIV, providers, and investigators in the current era. Potential mechanisms of HIV-related CNS dysfunction observed in patients treated with ART include persistent CNS infection, ongoing immune activation, effect of comorbidities including vascular disease, aging, antiretroviral drug exposure in the CNS associated with either toxicity or inadequate tissue distribution, and neurologic injury accrued prior to initiation of antiretroviral treatment. Related to issues of persistent clinical CNS abnormality in the face of ART, novel research questions are raised by efforts to successfully ‘cure’ HIV: whether the CNS may provide a reservoir for infection which may be a significant impediment to efforts to eradicate HIV. The pathobiology of this putative reservoir is under active investigation, including studies on the timing of establishment of CNS infection, the potential cells and tissues harboring HIV in the CNS, evidence of independent evolution of HIV in the CNS, and the possibility of autonomous CNS sources of HIV replication in the setting of suppressive therapy.

Wild grasses as the reservoirs of infection of rust species for winter soft wheat in the Northern Caucasus.

Common winter wheat is the main grain crop cultivated in the North Caucasus. Rust disease damage is one of the factors limiting wheat productivity. There are three species of rust in the region: leaf (Puccinia triticina), stem (P. graminis) and stripe rust (P. striiformis), and their signif icance varies from year to year. The most common is leaf rust, but in the last decade the frequency of its epiphytotic development has signif icantly decreased. At the same time, an increase in the harmfulness of stripe rust (P. striiformis) is noted. Stem rust in the region is mainly absent or observed at the end of the wheat growing season to a weak degree. Only in some years with favorable weather conditions its mass development is noted on susceptible cultivars. It is believed that the sources of infection with rust species in the North Caucasus are infested soft wheat crops, wild-growing cereals and exodemic infection carried by air currents from adjacent territories. In the North Caucasus, forage and wild grasses are affected by Puccinia species almost every year. Depending on weather conditions, the symptom expression is noted from late September to December and then from late February to May–June. Potentially, an autumn infection on grasses can serve as a source for infection of winter soft wheat cultivars sown in October. The purpose of these studies is to characterize the virulence of P. triticina, P. graminis, P. striiformis on wild cereals and to assess the specialization of causative agents to winter wheat in the North Caucasus. Infectious material represented by leaves with urediniopustules of leaf, stem and stripe rusts was collected from wild cereals (Poa spp., Bromus spp.) in the Krasnodar Territory in October–November 2019. Uredinium material from P. triticina, P. striiformis, and P. graminis was propagated and cloned. Monopustular Puccinia spp. isolates were used for virulence genetics analysis. In experiments to study the specialization of rust species from wild-growing cereals on common wheat, 12 winter cultivars were used (Grom, Tanya, Yuka, Tabor, Bezostaya 100, Yubileynaya 100, Vekha, Vassa, Alekseich, Stan, Gurt, Bagrat). These cultivars are widely cultivated in the North Caucasus region and are characterized by varying degrees of resistance to rust. Additionally, wheat material was inoculated with Krasnodar populations of P. triticina, P. striiformis, P. graminis from common wheat. In the virulence analysis of P. triticina on cereal grasses, four phenotypes (races) were identif ied: MCTKH (30 %), TCTTR (30 %), TNTTR (25 %), MHTKH (15 %), and f ive were identif ied in P. graminis (RKMTF (60 %), TKTTF, RKLTF, QKLTF, LHLPF (10 % each). Among P. striiformis isolates, three phenotypes were identif ied using the International and European sets of differentiating cultivars – 111E231 (88 %), 111E247 (6 %) and 78E199 (6 %). Using isogenic Avocet lines, 3 races were also identif ied, which differed among themselves in virulence to the Yr1, Yr11, Yr18 genes (with the prevalence of virulent ones (94 %)). Composite urediniums’ samples (a mixture of all identif ied races) of grass rust of each species were used to inoculate winter wheat cultivars. The most common winter wheat cultivars (75 %) were characterized by a resistant response when infected with P. graminis populations from common wheat and cereal grasses. All these cultivars were developed using donors of the rye translocation 1BL.1RS, in which the Lr26, Sr31, and Yr9 genes are localized. The number of winter wheat cultivars resistant to leaf rust in the seedling phase was lower (58 %). At the same time, all the studied cultivars in the seedling phase were susceptible to P. striiformis to varying degrees. The virulence analysis of the leaf, stem and stripe rust populations did not reveal signif icant differences in the virulence of the pathogens between wild-growing cereals and soft wheat. Urediniomaterial of all studied rust species successfully infested soft wheat cultivars. The results obtained indicate that grasses are rust infection reservoirs for common wheat crops in the North Caucasus.

The Current Status of Latency Reversing Agents for HIV-1 Remission.

Combinatory antiretroviral therapy (cART) reduces human immunodeficiency virus type 1 (HIV-1) replication but is not curative because cART interruption almost invariably leads to a rapid rebound of viremia due to the persistence of stable HIV-1-infected cellular reservoirs. These reservoirs are mainly composed of CD4+ T cells harboring replication-competent latent proviruses. A broadly explored approach to reduce the HIV-1 reservoir size, the shock and kill strategy, consists of reactivating HIV-1 gene expression from the latently infected cellular reservoirs (the shock), followed by killing of the virus-producing infected cells (the kill). Based on improved understanding of the multiple molecular mechanisms controlling HIV-1 latency, distinct classes of latency reversing agents (LRAs) have been studied for their efficiency to reactivate viral gene expression in in vitro and ex vivo cell models. Here, we provide an up-to-date review of these different mechanistic classes of LRAs and discuss optimizations of the shock strategy by combining several LRAs simultaneously or sequentially.

Targeting and Understanding HIV Latency: The CRISPR System against the Provirus.

The presence of latently infected cells and reservoirs in HIV-1 infected patients constitutes a significant obstacle to achieve a definitive cure. Despite the efforts dedicated to solve these issues, the mechanisms underlying viral latency are still under study. Thus, on the one hand, new strategies are needed to elucidate which factors are involved in latency establishment and maintenance. On the other hand, innovative therapeutic approaches aimed at eradicating HIV infection are explored. In this context, advances of the versatile CRISPR-Cas gene editing technology are extremely promising, by providing, among other advantages, the possibility to target the HIV-1 genome once integrated into cellular DNA (provirus) and/or host-specific genes involved in virus infection/latency. This system, up to now, has been employed with success in numerous in vitro and in vivo studies, highlighting its increasing significance in the field. In this review, we focus on the progresses made in the use of different CRISPR-Cas strategies to target the HIV-1 provirus, and we then discuss recent advancements in the use of CRISPR screens to elucidate the role of host-specific factors in viral latency.

HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.

Human immunodeficiency virus (HIV)-infected people's livelihoods are gradually being prolonged with the use of combined antiretroviral therapy (ART). Conversely, despite viral suppression by ART, the symptoms of HIV-associated neurocognitive disorder (HAND) endure. HAND persists because ART cannot really permanently confiscate the virus from the body. HAND encompasses a variety of conditions based on clinical presentation and severity level, comprising asymptomatic neurocognitive impairment, moderate neurocognitive disorder, and HIV-associated dementia. During the early stages of HIV infection, inflammation compromises the blood-brain barrier, allowing toxic virus, infected monocytes, macrophages, T-lymphocytes, and cellular products from the bloodstream to enter the brain and eventually the entire central nervous system. Since there are no resident T-lymphocytes in the brain, the virus will live for decades in macrophages and astrocytes, establishing a reservoir of infection. The HIV proteins then inflame neurons both directly and indirectly. The purpose of this review is to provide a synopsis of the effects of these proteins on the central nervous system and conceptualize avenues to be considered in mitigating HAND. We used bioinformatics repositories extensively to simulate the transcription factors that bind to the promoter of the HIV-1 protein and possibly could be used as a target to circumvent HIV-associated neurocognitive disorders. In the same vein, a protein-protein interaction complex was also deduced from a Search Tool for the Retrieval of Interacting Genes. In conclusion, this provides an alternative strategy that could be used to avert HAND.

The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya

BackgroundFurther reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission.MethodsIn a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa–Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals.ResultsThe prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR.ConclusionsThis assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.

Isolation and molecular identification of Acanthamoeba spp. from hospital dust and soil of Khomein, Iran, as reservoir for nosocomial infection.

BackgroundAcanthamoeba spp. are commonest opportunistic amoebae, which ubiquitous in various environmental resources. Acanthamoeba species are the causative agents of amoebic keratitis, granulomatous amoebic encephalitis and i.e. in immunocompromised and immunocompetent patients. Moreover Acanthamoeba spp. can act as reservoir and transmission agent of bacterial pathogens. Due to this issue the aim of this study was to characterized Acanthamoeba spp. genotypes in dust and soil of hospital samples from Khomein of Iran. MethodsIn a cross sectional study, a total of 100 soil and dust samples were collected from hospital environment of Khomein Iran, and analyzed for the presence of Acanthamoeba spp. based on phenotypic and molecular methods including PCR amplification and sequence analysis of 18SrRNA. A total of 5 Acanthamoeba isolates were sequenced, and different genotypes of isolates were detected via direct sequence analysis. ResultsThe results showed that 20% of samples (20/100) were positive for Acanthamoeba, while only 5 cases were successfully cultured in NNM medium and were subjected to molecular assay. A. lenticulata, A. castellanii and A. quina were the prevalent identified species that were belonged to T4 and T5 genotypes. ConclusionsAcanthamoeba spp. are the most prevalent free living amoeba in the dust and soil of hospital environment. Moreover, due to the presence of potentially pathogenic T4 genotypes in our hospital, it is recommended that in health and hygienic programs elimination of FLA should be considered.

Engaging frontline providers: an important key to eliminating tuberculosis in Canada, and other high-income countries.

The greatest human cost of the rapidly moving pandemic of SARS-CoV-2 may be due to its impact on the response to other diseases. One such other disease is tuberculosis (TB). All indications suggest that COVID-19-related diversions of healthcare resources and disruptions to public health programming will exacerbate the slower moving pandemic of TB. This is expected to set back TB elimination efforts by years. This is a prediction that is especially relevant to Canada, which has repeatedly failed to meet pre-set targets for the elimination of TB even before the COVID-19 pandemic began. A collaborative approach to achieve TB elimination, one that engages all care providers, has recently been emphasized by the STOP-TB Partnership. Among TB elimination strategies, frontline providers (e.g., family physicians, emergency room physicians, and others) are well positioned to identify candidates for the treatment of latent TB infection, and make the diagnosis of infection-spreading cases of TB in a timely manner, thereby interrupting forward-moving chains of transmission. Electronic medical records offer the promise of automating these processes. In this commentary, we promote broader engagement of the workforce across multiple sectors of medicine to reduce TB associated morbidity and mortality, interrupt transmission, and shrink the reservoir of latent TB infection.

ИНФИЦИРОВАННОСТЬ ДЕТЕЙ МИКОБАКТЕРИЯМИ ТУБЕРКУЛЁЗА В ОЧАГАХ ТУБЕРКУЛЁЗНОЙ ИНФЕКЦИИ РЕСПУБЛИКИ ТАДЖИКИСТАН

To study the prevalence of Mycobacterium tuberculosis at the infection reservoirs in the Republic of Tajikistan among children and the impact of BCG vaccination assessed by tuberculin skin test.

Wolf in Sheep's Clothing: Clostridioides difficile Biofilm as a Reservoir for Recurrent Infections.

The microbiota inhabiting the intestinal tract provide several critical functions to its host. Microorganisms found at the mucosal layer form organized three-dimensional structures which are considered to be biofilms. Their development and functions are influenced by host factors, host-microbe interactions, and microbe-microbe interactions. These structures can dictate the health of their host by strengthening the natural defenses of the gut epithelium or cause disease by exacerbating underlying conditions. Biofilm communities can also block the establishment of pathogens and prevent infectious diseases. Although these biofilms are important for colonization resistance, new data provide evidence that gut biofilms can act as a reservoir for pathogens such as Clostridioides difficile. In this review, we will look at the biofilms of the intestinal tract, their contribution to health and disease, and the factors influencing their formation. We will then focus on the factors contributing to biofilm formation in C. difficile, how these biofilms are formed, and their properties. In the last section, we will look at how the gut microbiota and the gut biofilm influence C. difficile biofilm formation, persistence, and transmission.

MERS-CoV in sheep, goats, and cattle, United Arab Emirates, 2019: Virological and serological investigations reveal an accidental spillover from dromedaries.

The recent COVID-19 pandemic has demonstrated again the global threat posed by emerging zoonotic coronaviruses. During the past two decades alone, humans have experienced the emergence of several coronaviruses, such as SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019. To date, MERS-CoV has been detected in 27 countries, with a case fatality ratio of approximately 34.5%. Similar to other coronaviruses, MERS-CoV presumably originated from bats; however, the main reservoir and primary source of human infections are dromedary camels. Other species within the Camelidae family, such as Bactrian camels, alpacas, and llamas, seem to be susceptible to the infection as well, although to a lesser extent. In contrast, susceptibility studies on sheep, goats, cattle, pigs, chickens, and horses obtained divergent results. In the present study, we tested nasal swabs and/or sera from 55 sheep, 45 goats, and 52 cattle, collected at the largest livestock market in the United Arab Emirates, where dromedaries are also traded, for the presence of MERS-CoV nucleic acid by RT-qPCR, and for specific antibodies by immunofluorescence assay. All sera were negative for MERS-CoV-reactive antibodies, but the nasal swab of one sheep (1.8%) repeatedly tested positive for MERS-CoV nucleic acid. Next generation sequencing (NGS) of the complete N gene of the sheep-derived MERS-CoV revealed>99% nucleotide identity to MERS-CoV sequences of five dromedaries in nearby pens and to three reference sequences. The NGS sequence of the sheep-derived MERS-CoV was confirmed by conventional RT-PCR of a part of the N gene and subsequent Sanger sequencing. All MERS-CoV sequences clustered within clade B, lineage 5. In conclusion, our study shows that noncamelid livestock, such as sheep, goats, and cattle do not play a major role in MERS-CoV epidemiology. The one sheep that tested positive most likely reflects an accidental viral spillover event from infected dromedaries in nearby pens.

Reservoir dynamics of rabies in south-east Tanzania and the roles of cross-species transmission and domestic dog vaccination.

Understanding the role of different species in the transmission of multi-host pathogens, such as rabies virus, is vital for effective control strategies. Across most of sub-Saharan Africa domestic dogs Canis familiaris are considered the reservoir for rabies, but the role of wildlife has been long debated. Here we explore the multi-host transmission dynamics of rabies across south-east Tanzania.Between January 2011 and July 2019, data on probable rabies cases were collected in the regions of Lindi and Mtwara. Hospital records of animal-bite patients presenting to healthcare facilities were used as sentinels for animal contact tracing. The timing, location and species of probable rabid animals were used to reconstruct transmission trees to infer who infected whom and the relative frequencies of within- and between-species transmission.During the study, 688 probable human rabies exposures were identified, resulting in 47 deaths. Of these exposures, 389 were from domestic dogs (56.5%) and 262 from jackals (38.1%). Over the same period, 549 probable animal rabies cases were traced: 303 in domestic dogs (55.2%) and 221 in jackals (40.3%), with the remainder in domestic cats and other wildlife species.Although dog-to-dog transmission was most commonly inferred (40.5% of transmission events), a third of inferred events involved wildlife-to-wildlife transmission (32.6%), and evidence suggested some sustained transmission chains within jackal populations.A steady decline in probable rabies cases in both humans and animals coincided with the implementation of widespread domestic dog vaccination during the first 6 years of the study. Following the lapse of this program, dog rabies cases began to increase in one of the northernmost districts. Synthesis and applications. In south-east Tanzania, despite a relatively high incidence of rabies in wildlife and evidence of wildlife-to-wildlife transmission, domestic dogs remain essential to the reservoir of infection. Continued dog vaccination alongside improved surveillance would allow a fuller understanding of the role of wildlife in maintaining transmission in this area. Nonetheless, dog vaccination clearly suppressed rabies in both domestic dog and wildlife populations, reducing both public health and conservation risks and, if sustained, has potential to eliminate rabies from this region.

Enterococcal Endocarditis: Hiding in Plain Sight.

Enterococcus faecalis is a major opportunistic bacterial pathogen of increasing clinical relevance. A substantial body of experimental evidence suggests that early biofilm formation plays a critical role in these infections, as well as in colonization and persistence in the GI tract as a commensal member of the microbiome in most terrestrial animals. Animal models of experimental endocarditis generally involve inducing mechanical valve damage by cardiac catheterization prior to infection, and it has long been presumed that endocarditis vegetation formation resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage. Here we review both historical and contemporary animal model studies demonstrating the robust ability of E. faecalis to directly attach and form stable microcolony biofilms encased within a bacterially-derived extracellular matrix on the undamaged endovascular endothelial surface. We also discuss the morphological similarities when these biofilms form on other host tissues, including when E. faecalis colonizes the GI epithelium as a commensal member of the normal vertebrate microbiome - hiding in plain sight where it can serve as a source for systemic infection via translocation. We propose that these phenotypes may allow the organism to persist as an undetected infection in asymptomatic individuals and thus provide an infectious reservoir for later clinical endocarditis.

Contamination of Hospital Surfaces with Bacterial Pathogens under the Current COVID-19 Outbreak.

The SARS-CoV-2 pandemic remains a global health issue for several reasons, such as the low vaccination rates and a lack of developed herd immunity to the evolution of SARS-CoV-2, as well as its potential inclination to elude neutralizing antibodies. It should be noted that the severity of the COVID-19 disease is significantly affected by the presence of co-infections. Comorbid conditions are caused not only by pathogenic and opportunistic microorganisms but also by some representatives of the environmental microbiome. The presence of patients with moderate and severe forms of the disease in hospitals indicates the need for epidemiological monitoring of (1) bacterial pathogens circulating in hospitals, especially the ESKAPE group pathogens, and (2) the microbiome of various surfaces in hospitals. In our study, we used combined methods based on PCR and NGS sequencing, which are widely used for epidemiological monitoring. Through this approach, we identified the DNA of pathogenic bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, CoNS, and Achromobacter spp.) on various surfaces. We also estimated the microbiome diversity of surfaces and identified the potential reservoirs of infections using 16S rRNA profiling. Although we did not assess the viability of identified microorganisms, our results indicate the possible risks of insufficient regular disinfection of surfaces, regardless of department, at the Infectious Diseases Hospital. Controlling the transmission of nosocomial diseases is critical to the successful treatment of COVID-19 patients, the rational use of antimicrobial drugs, and timely decontamination measures.

Circulating Brucella species in wild animals of the Serengeti ecosystem, Tanzania

BackgroundBrucellosis is a bacterial zoonosis of public health and economic importance worldwide. It affects a number of domestic animals, wild animals and humans. Human brucellosis originates from either livestock or wildlife. The species of Brucella circulating in wild animals in Tanzania is largely unknown due to insufficient surveillance. This study was carried out to identify Brucella species found in selected wildlife hosts in the Serengeti ecosystem.MethodologyThe study used a total of 189 archived samples that were obtained from cross-sectional studies previously conducted between 2000 and 2017 in the Serengeti ecosystem in Tanzania. Whole blood, serum and amniotic fluid collected from buffalos, lions, wildebeest, impala, zebra and hyena were available for DNA extraction. Multiplex polymerase chain reaction for B. abortus, B. melitensis, B. ovis and B. suis (AMOS PCR) and quantitative real-time PCR (qPCR) targeting the bcsp31 and IS711 genes for Brucella genus detection and the IS711 targets alkB for B. abortus and BMEI1162 for B. melitensis were used to detect Brucella strains.ResultsOut of the 189 samples tested, 12 (6.35 %) and 22 (11.6 %) were positive to AMOS-PCR and qPCR, respectively. Most of the positive samples were from lions (52.6 %) and buffaloes (19.6 %). Other animals that were positive included: wildebeest (13.6 %), impala (13.6 %), zebra (4.5 %) and hyena (4.5 %). Out of 22 positive samples, 16 (66.7 %) were identified as B. abortus and the other six samples did not amplify for neither B. abortus nor B. melitensis.ConclusionsThe detection of Brucella DNA in archived wild animal samples shows testing potential of samples collected from this population. The zoonotic species B. abortus and B. melitensis detected in wild animals have previously been reported in livestock and humans in the region. The findings suggest that, due to the contact network, some of the identified wild animal hosts in this study could be reservoirs for infections in domestic animals and humans within the Serengeti ecosystem while others are likely dead-end hosts. One Health control strategies and continuous surveillance programs in other wildlife reserved areas should be implemented to help predicting transmission in livestock and humans in the region.

Self-Reported Gum Bleeding in COVID-19 Patients: A Questionnaire-Based Study

Background: Coronavirus disease 2019 (COVID-19) has affected a huge number of people around the world. It has increased worldwide mortality and morbidity and is accompanied by different signs and symptoms. Some researchers have linked oral manifestations as introductory signs for COVID-19, such as vesiculobullous lesions, non-specific stomatitis, and oral ulcers. The oral cavity has been perceived as a potential reservoir for asymptomatic COVID-19 infection, specifically the salivary glands and the oral mucosa. This study builds on a previous case report by the authors on COVID-19 associated gingival bleeding in an attempt to investigate the generalization of this relation. Methods: A cross-sectional survey based on a struc­tured, pre-tested, and validated questionnaire that was adapted and modified by the authors was carried out electronically for a minimal sample size of patients that was calculated for this study beforehand. This study was approved by the Batterjee Medical College ethical committee and data collection followed a structured criteria and a clear work plan based on the established inclusion criteria. Results: The questionnaire had a high response rate of 315 participants. 63.2% (n=199) reported gum bleeding during virus infection time – 25.6% (n=51) of whom reported that this symptom was present prior to COVID-19 infection. 88.9% (n=177) of participants reported only mild bleeding. Gingival bleeding was more prevalent among females 63.8% (n=127) compared to males 36.2% (n=72) (odds ratio: 0.859 [95% CI, 0.530 to 1.394]). Conclusion: Gingival bleeding may be considered as one of the signs of COVID-19 and is a prevalent symptom as reported by infected patients. However, a larger sample size and investigation of hospitalized moderate and severe cases of the disease would help elucidate the actual association.

Cytomegalovirus infection in malignant pleural mesothelioma.

Human cytomegalovirus (HCMV) is a highly prevalent herpes virus which persists as a latent infection and has been detected in several different tumor types. HCMV disease is rare but may occur in high-risk settings, often manifesting as a pulmonary infection. To date HCMV has not been investigated in malignant pleural mesothelioma (MPM). In a consecutive case series of 144 MPM patients we evaluated two biomarkers of HCMV: IgG serostatus (defined as positive and negative) and DNAemia (>100 copies/mL of cell free HCMV DNA in serum). Approximately half of the MPM patient population was HCMV IgG seropositive (51%). HCMV DNAemia was highly prevalent (79%) in MPM and independent of IgG serostatus. DNAemia levels consistent with high level current infection (>1000 copies/mL serum) were present in 41% of patients. Neither IgG serostatus nor DNAemia were associated with patient survival. In tissues, we observed that HCMV DNA was present in 48% of tumors (n = 40) and only 29% of normal pleural tissue obtained from individuals without malignancy (n = 21). Our results suggest nearly half of MPM patients have a high level current HCMV infection at the time of treatment and that pleural tissue may be a reservoir for latent HCMV infection. These findings warrant further investigation to determine the full spectrum of pulmonary infections in MPM patients, and whether treatment for high level current HCMV infection may improve patient outcomes.

High prevalence of Plasmodium malariae and Plasmodium ovale in co-infections with Plasmodium falciparum in asymptomatic malaria parasite carriers in southwestern Nigeria

Asymptomatic malaria parasite carriers do not seek anti-malarial treatment and may constitute a silent infectious reservoir. In order to assess the level of asymptomatic and symptomatic carriage amongst adolescents in a highly endemic area, and to identify the risk factors associated with such carriage, we conducted a cross-sectional survey of 1032 adolescents (ages 10–19 years) from eight schools located in Ibadan, southwestern Nigeria in 2016. Blood films and blood spot filter paper samples were prepared for microscopy and DNA analysis. The prevalence of asymptomatic malaria was determined using microscopy, rapid diagnostic tests and PCR for 658 randomly selected samples. Of these, we found that 80% of asymptomatic schoolchildren were positive for malaria parasites by PCR, compared with 47% and 9%, determined by rapid diagnostic tests and microscopy, respectively. Malaria parasite species typing was performed using PCR targeting the mitochondrial CoxIII gene, and revealed high rates of carriage of Plasmodium malariae (53%) and Plasmodium ovale (24%). Most asymptomatic infections were co-infections of two or more species (62%), with Plasmodium falciparum + P. malariae the most common (35%), followed by P. falciparum + P. malariae + P. ovale (21%) and P. falciparum + P. ovale (6%). Single infections of P. falciparum, P. malariae and P. ovale accounted for 24%, 10% and 4% of all asymptomatic infections, respectively. To compare the species composition of asymptomatic and symptomatic infections, further sample collection was carried out in 2017 at one of the previously sampled schools, and at a nearby hospital. Whilst the species composition of the asymptomatic infections was similar to that observed in 2016, the symptomatic infections were markedly different, with single infections of P. falciparum observed in 91% of patients, P. falciparum + P. malariae in 5% and P. falciparum + P. ovale in 4%.

Antibiotic tolerance in biofilm persister cells of Staphylococcus aureus and expression of toxin-antitoxin system genes

The ability of Staphylococcus aureus to form biofilm and persister cells is the main cause of recurrent infections. This study aimed to evaluate the expression of toxin-antitoxin (TA) systems in persister cells within S. aureus biofilms. Time-dependent variation in the persister population present in biofilms of S. aureus was examined after treatment with bactericidal antibiotics. Then, the relative expression level of type II TA system (mazF, relE1, and relE2), type I TA system (sprG), and clpP protease genes in S. aureus strains were assessed by Real _Time PCR. Among the sixteen isolates, two isolates were found to be the strongest biofilm producers. The established biofilm of these isolates showed a comparable biphasic pattern at the lethal dose of the antibiotics. The expression level of TA system genes was increased and strain-specific expression patterns were observed under antibiotics stress conditions. Persisters within a biofilm may establish a reservoir for relapsing infection and could contribute to treatment failures. Hence, the possible role of the TA systems should be considered in biofilm and persister cell formation.

Impact of IRS: Four-years of entomological surveillance of the Indian Visceral Leishmaniases elimination programme.

In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016. Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS. Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019. Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets.