MicrobiologyBytes

The risk of tuberculosis (TB) and latent TB (in which the bacteria that cause TB lie dormant but can reactivate later to cause active TB disease) is higher in the prison population than in the general population. And importantly, the spread of TB and latent TB within prisons can substantially increase their incidence in the general population. These findings suggest that improvements in prison TB control would not only help to protect prisoners and staff from within-prison spread of TB, but would also reduce national TB burdens. Using previous findings from published studies and data from the World Health Organization, the authors calculated the ratio between the incidence rates for TB and latent TB in prison and in the general population. The average incidence of TB in prisons was 23 times higher that of the general population, and for latent TB, was 26 times higher in prisons than in the general population. The authors also estimated the fraction of TB in the general population attributable to within-prison exposure to TB and found that, on average, the population attributable fraction for TB in high-income countries was 8.5%; in middle-to-low–income countries, the average the population attributable fraction for TB was 6.3%.

The authors say: “These data may prove useful to inform the development of rational policies to control TB transmission in correctional facilities.” They add: “Future studies should assess the population attributable risk of prison-to-community spread and describe the conditions in the prison that influence TB transmission.” In an accompanying editorial, the PLoS Medicine editors conclude: “The publication of this systematic review marks a shift from considering the incidence of TB in each prison population to considering the massive global impact of tuberculosis in prisons.”

Tuberculosis Incidence in Prisons: A Systematic Review. (2010) PLoS Med 7(12): e1000381.doi:10.1371/journal.pmed.1000381

Related:

1. Why is TB more common in men than in women?
2. Origin and spread of Mycobacterium tuberculosis
3. Tuberculosis – is the white plague winning?

Emerging pathogens cause new or previously unrecognized diseases, and among them, emerging zoonotic diseases are a major concern among scientists studying infectious diseases at different spatial and temporal scales. Changes in conditions may alter population disease dynamics and lead to the emergence of zoonotic infections. During the last decades, several outbreaks of emerging and re-emerging viral pathogens have occurred, affecting both purely-local and worldwide/pandemic involvement of human populations. Among the conspicuous examples are influenza A, Ebola virus, hepatitis C virus, severe adult respiratory distress (SARS), coronavirus, and human immunodeficiency virus, which challenge prevention and control measures of public health systems. In the Americas, the recent outbreak of pandemic influenza A subtype H1N1 became a major target for control due to its rapid spread, and uncertainties in virulence and transmissibility, yet vaccine availability was limited when significant activity occurred in advance of the traditional influenza season. However, in the last century outbreaks of several viral-related diseases have emerged or re-emerged involving arenaviruses and dengue viruses, and more recently, hantaviruses, and the expansion of the geographic range of West Nile virus. Among zoonotic diseases, small mammals are hosts of several pathogenic RNA viruses, especially Arenaviridae and Bunyaviridae.

Hantaviruses in the Americas and Their Role as Emerging Pathogens. Viruses. 2010; 2(12): 2559-2586. doi:10.3390/v2122559
The continued emergence and re-emergence of pathogens represent an ongoing, sometimes major, threat to populations. Hantaviruses (family Bunyaviridae) and their associated human diseases were considered to be confined to Eurasia, but the occurrence of an outbreak in 1993–94 in the southwestern United States led to a great increase in their study among virologists worldwide. Well over 40 hantaviral genotypes have been described, the large majority since 1993, and nearly half of them pathogenic for humans. Hantaviruses cause persistent infections in their reservoir hosts, and in the Americas, human disease is manifest as a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS), with case-fatality ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity.

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• Unknown disease in South Africa identified as arenavirus infection
• A new arenavirus associated with hemorrhagic fever
• Where do viruses come from?

Candida albicans is the predominant fungal pathogen of humans. In healthy individuals C. albicans is a commensal inhabitant of the gastrointestinal, oral and vaginal tracts. C. albicans can cause superficial infections which, although not life threatening, provide discomfort to the individual and require treatment with antifungals which is a constant drain on hospitals resources. However, C. albicans infections are life threatening when the individual’s immune system becomes compromised as a result of age, cancer, chemotherapy hospitalisation and AIDS. Under these circumstances superficial infections may readily develop into systemic disease where mortality rates are reported to be up to 40%, which is higher than those for most bacterial infections.

Pathogenic microorganisms can produce a variety of secondary metabolites and signalling molecules which can affect the host, or provide them with a selective advantage against competing commensal organisms. This paper demonstrates that gaseous, metabolically generated CO₂ can serve as a signalling molecule to enhance the organism’s virulence during infection establishment by using the fungal pathogen Candida albicans as a model. The researchers identified a CO₂ receptor site within the catalytic domain of the soluble adenylyl cyclase, Cyr1p, which is critical for CO₂ sensing and hence virulence of the organism. CO₂ sensing is conserved in a variety of pathogenic species, and increased levels have been shown to suppress the host’s immune system. CO₂ sensing may represent a mechanism to enhance C. albicans virulence when the host’s immune system is suppressed.

CO₂ Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans. (2010) PLoS Pathog 6(11): e1001193. doi:10.1371/journal.ppat.1001193
When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO₂ acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO₂-mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO₂/bicarbonate regulation of Cyr1p. Disruption of the CO₂/bicarbonate receptor-site interferes selectively with C. albicans filamentation within fungal biomasses. Comparisons between the Drosophila melanogaster infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO₂ sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous Candida signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO₂-signalling system.

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• New Mechanism Fundamental to the Spread of Invasive Yeast
• Statins and Candida

Chlamydia is the most prevalent bacterial sexually transmitted infection (STI) in the western world. In Ireland, the number of chlamydia notifications increased from 245 in 1995 to 6290 in 2008. While this may reflect a real rise in the burden of chlamydia infection, it also reflects an increase in provider awareness in chlamydia testing, test performance and the introduction of laboratory notification. The real burden (numbers of infection) is likely to be higher than reported as chlamydia is asymptomatic in approximately 70% of women and 50% of men and thus may remain undiagnosed. Prevalence studies in young Irish people (including students) have shown similar rates of infection to the UK and else where in Europe.

In view of the asymptomatic nature of chlamydia, especially in women, there is recognition that it is important to screen sexually active women aged less than 25 years. Two approaches are proposed: systematic, where all eligible young persons are systematically invited for screening, which requires the availability of a unique identifier for each individual to ensure all eligible persons are invited and not invited again except where indicated; and opportunistic, where eligible young persons that are visiting/utilising clinical and non-clinical settings are invited to take a test.

These issues highlight the need for additional strategies for screening that are free at the point of testing, easy to access, private and available in a variety of settings. Screening strategies need to be ‘youth friendly’ and available outside of traditional medical facilities.

Pee-in-a-Pot: acceptability and uptake of on-site chlamydia screening in a student population in the Republic of Ireland. (2010) BMC Infectious Diseases 10: 325 doi:10.1186/1471-2334-10-325
Background: The aim of the study was to explore the acceptability and uptake of on-campus screening using a youth friendly approach in two Third Level higher education institutions (HEIs). This study is part of wider research exploring the optimal setting for chlamydia screening in Ireland.
Methods: Male and female students were given the opportunity to take a free anonymous test for chlamydia during a one week programme of “pee-in-a-pot” days at two HEI campuses in the West of Ireland. The study was set up after extensive consultation with the two HEIs and advertised on the two campuses using a variety of media in the two weeks preceding the screening days. Screening involved the provision and distribution of testing packs at communal areas and in toilet facilities. In Ireland, chlamydia notifications are highest amongst 20-29 year olds and hence the screening criterion was aimed at 18-29 year olds. Urine samples were tested using a nucleic acid amplification test (NAAT). Following the screening days, qualitative in-depth interviews were conducted with participants about their experiences of the event.
Results: Out of 1,249 test kits distributed in two HEIs, 592 specimens were collected giving a return rate of 47.5%. Tests excluded (54) were due to labelling errors or ineligibility of participants’ age. Two thirds of those tested were females and the mean age was 21 years. Overall, 3.9% (21/538) of participants tested positive, 5% (17/336) among females and 2% (4/191) among males. Participant interviews identified factors which enhanced student participation such as anonymity, convenience, accessibility of testing, and the informal and non-medical approach to testing.
Conclusions: Screening for chlamydia using on-campus “pee-in-a-pot” days is an acceptable strategy in this population. This model can detect and treat asymptomatic cases of chlamydia and avoid many of the barriers associated with testing for sexually transmitted infections (STIs) in clinical settings.

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• Telling partners about chlamydia – how ?
• Chlamydia Infection
• UK chlamydia cases up in under-16s
• Low uptake of Chlamydia screening in the UK

From the outside and within, we are constantly bombarded with a myriad of diverse microbial species. However, our bodies are equipped with an evolutionarily conserved innate immune defense system that allows us to thwart potential pathogens. Antimicrobial peptides (AMPs) are a unique and assorted group of molecules produced by living organisms of all types, considered to be part of the host innate immunity. These peptides demonstrate potent antimicrobial activity and are rapidly mobilized to neutralize a broad range of microbes, including viruses, bacteria, protozoa, and fungi. More significantly, the ability of these natural molecules to kill multidrug-resistant microorganisms has gained them considerable attention and clinical interest. With the growing microbial resistance to conventional antimicrobial agents, the need for unconventional therapeutic options has become urgent. This article provides an overview of AMPs, their biological functions, mechanism of action, and applicability as alternative therapeutic agents.

Presently, AMPs represent one of the most promising future strategies for combating infections and microbial drug resistance. This is evident by the increasing number of studies to which these peptides are subjected. As our need for new antimicrobials becomes more pressing, the question remains: can we develop novel drugs based on the design principles of primitive molecules?

Antimicrobial Peptides: Primeval Molecules or Future Drugs? (2010) PLoS Pathog 6(10): e1001067. doi:10.1371/journal.ppat.1001067

Related:

• Antimicrobial Peptides
• Frogs vs Bacteria

Dengue virus infection is a growing public health problem with up to 100 million cases annually, and neither vaccines nor effective therapies are available. To search for the ways of preventing and treating dengue infections we need to better understand their molecular mechanisms. As with many other viruses, dengue virus enters cells by fusion between the viral membrane and the membrane of intracellular vesicles (endosomes). In this paper the authors explore the fusion stage of dengue virus entry in different experimental systems ranging from virus fusion to artificial lipid membranes to fusion inside the cells. While earlier work on dengue virus entry has focused on the virus protein that mediates fusion, they found that effective action of this protein requires specific lipid composition of the membrane the virus fuses to. In effect, this lipid dependence allows virus to control intracellular location of the fusion event and, thus, the place of its RNA release by exploiting cell-controlled differences between lipid compositions of different organelles the virus travels through. The essential role of the interactions between dengue virus and its lipid cofactors during virus entry suggests that these interactions may be targeted in drug design.

Dengue Virus Ensures Its Fusion in Late Endosomes Using Compartment-Specific Lipids. PLoS Pathog 6(10): e1001131. doi:10.1371/journal.ppat.1001131
Many enveloped viruses invade cells via endocytosis and use different environmental factors as triggers for virus-endosome fusion that delivers viral genome into cytosol. Intriguingly, dengue virus (DEN), the most prevalent mosquito-borne virus that infects up to 100 million people each year, fuses only in late endosomes, while activation of DEN protein fusogen glycoprotein E is triggered already at pH characteristic for early endosomes. Are there any cofactors that time DEN fusion to virion entry into late endosomes? Here we show that DEN utilizes bis(monoacylglycero)phosphate, a lipid specific to late endosomes, as a co-factor for its endosomal acidification-dependent fusion machinery. Effective virus fusion to plasma- and intracellular- membranes, as well as to protein-free liposomes, requires the target membrane to contain anionic lipids such as bis(monoacylglycero)phosphate and phosphatidylserine. Anionic lipids act downstream of low-pH-dependent fusion stages and promote the advance from the earliest hemifusion intermediates to the fusion pore opening. To reach anionic lipid-enriched late endosomes, DEN travels through acidified early endosomes, but we found that low pH-dependent loss of fusogenic properties of DEN is relatively slow in the presence of anionic lipid-free target membranes. We propose that anionic lipid-dependence of DEN fusion machinery protects it against premature irreversible restructuring and inactivation and ensures viral fusion in late endosomes, where the virus encounters anionic lipids for the first time during entry. Currently there are neither vaccines nor effective therapies for DEN, and the essential role of the newly identified DEN-bis(monoacylglycero)phosphate interactions in viral genome escape from the endosome suggests a novel target for drug design.

Related:

• Dengue Virus
• Pathogenesis and treatment of dengue fever

Measles is a common infection in children and is spread by the respiratory route, but where did the virus come from? The disease is characterized by a prodromal (initial) illness of fever, coryza, cough, and conjunctivitis followed by appearance of a generalized maculopapular rash. Measles virus (MeV) infects approximately 30 million people annually, with a mortality of 197,000, mainly in developing countries. In the prevaccine era, more than 90% of 15-year-old children had a history of measles. Measles remains a major cause of mortality in children, particularly in areas with inadequate vaccination and medical care.

MeV infection can confer lifelong immunity, and there is no animal reservoir or evidence of latent or common persistent infection except for a rare condition called subacute sclerosing panencephalitis (SSPE). Therefore, maintenance of MeV in a population requires constant supply of susceptible individuals. If the population is too small to establish continuous transmission, the virus can be eliminated. Mathematical analysis shows that an immunologically-naïve population of 250,000-500,000 is needed to maintain MeV. This is approximately the population of the earliest urban civilizations in ancient Middle Eastern river valleys around 3000-2500 BCE. Historically, the first scientific description of measles-like syndrome was provided by Abu Becr, known as Rhazes, in the 9th century. However, smallpox was accurately described by Galen in the 2nd second century whereas measles was not. Epidemics identified as measles were recorded in the 11th and 12th centuries.

MeV is a member of the genus Morbillivirus, which belongs to the family Paramyxoviridae. In addition to MeV, Morbillivirus includes dolphin and porpoise morbillivirus, canine distemper virus, phocid distemper virus, peste des petits ruminants virus, and rinderpest virus (RPV). Genetically and antigenetically, MeV is most closely related to RPV, which is a pathogen of cattle. MeV is assumed to have evolved in an environment where cattle and humans lived in close proximity. MeV probably evolved after commencement of livestock farming in the early centers of civilization in the Middle East. The speculation agrees with the mathematical analysis mentioned above.

Molecular clock analysis can estimate the age of ancestors in evolutionary history by phylogenetic patterns. The basic approach to estimating molecular dates is to measure the genetic distance between species and use a calibration rate (the number of genetic changes expected per unit time) to convert the genetic distance to time. Pomeroy et al. showed that “Time to the Most Recent Common Ancestor” of the current MeV circulating worldwide is recent, i.e., within the last century (around 1943). Nevertheless, the time when MeV was introduced to human populations has not been investigated. In this study, the researchers performed molecular clock analysis on MeV to determine the time of divergence from RPV, suggesting that MeV emerged in humans in the 11th to 12th centuries.

Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries. Virology Journal 2010, (7):52 doi:10.1186/1743-422X-7-52
Measles, caused by measles virus (MeV), is a common infection in children. MeV is a member of the genus Morbillivirus and is most closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV is thought to have evolved in an environment where cattle and humans lived in close proximity. Understanding the evolutionary history of MeV could answer questions related to divergence times of MeV and RPV. We investigated divergence times using relaxed clock Bayesian phylogenetics. Our estimates reveal that MeV had an evolutionary rate of 6.0 – 6.5×10^-4 substitutions/site/year. It was concluded that the divergence time of the most recent common ancestor of current MeV was the early 20th century. And, divergence between MeV and RPV occurred around the 11th to 12th centuries. The result was unexpected because emergence of MeV was previously considered to have occurred in the prehistoric age. MeV may have originated from virus of non-human species and caused emerging infectious diseases around the 11th to 12th centuries. In such cases, investigating measles would give important information about the course of emerging infectious diseases.

Related:

• Emerging and re-emerging infectious diseases
• Measles vaccination and SSPE

Even if we have never succumbed to it, we are all familiar with the sickness caused by noroviruses due to high-profile media coverage of outbreaks in various closed communities, such as hospitals and cruise ships. In this article in Microbiology Today, Ian Goodfellow and David Brown ask, how extensive are noroviruses in our food chain and what can be done to prevent outbreaks in future?

In the catering industry, education of food handlers is key. Clear guidelines for good practice in food preparation need to be strictly adhered to and policed. Whilst it is generally accepted that there remains an ongoing risk from oysters, etc, since sewage contamination of estuarine waters is likely to continue and depuration is ineffective for viruses, the development of sensitive screening procedures for identifying contamination has the potential to reduce the risk. Further improvements in decontamination of contaminated food and environmental settings will undoubtedly aid in minimizing the effects of norovirus contamination and outbreaks. Until such times that vaccines and/or antivirals are available, as consumers, good hygiene and common sense are the most effective protection against norovirus infection, i.e. increased hand washing, as well as avoidance of shared food sources/ utensils and pre-prepared food during outbreaks.

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Related:

• Pathogenesis of Noroviruses
• How Noroviruses cause repeated outbreaks of gastroenteritis
• Norovirus evasion of the immune system

In the past three years, remarkable discoveries have added three new human polyomaviruses (KI virus (KIV), WU virus (WUV) and Merkel cell virus (MCV)) to a class that previously had only two disease-causing members (BK virus (BKV) and JC virus (JCV)) identified. Two monkey polyomaviruses, simian virus (SV)40 and B-cell lymphotropic polyomavirus (LPV) are also present in humans. KIV and WUV lack the agnoprotein coding sequence and regulatory micro (mi)RNA clusters of BKV, JCV and SV40. MCV lacks the agnoprotein sequence but generates miRNAs. KIV, WUV and MCV are all widespread in humans. Although they have distinctive tissue tropisms, all these viruses are probably acquired in childhood. Of these viruses, only MCV has thus far been strongly linked to cancer. Marshalled evidence from diverse sources implicates MCV as an etiological agent of Merkel cell carcinoma. This review compares the structural features of the new and previously known polyomaviruses, with the aim of identifying approaches to molecular pathology.

Structural evaluation of new human polyomaviruses provides clues to pathobiology. Trends Microbiol. 2010 18(5): 215-223

Related:

• High prevalence of infection with three new human polyomaviruses
• Polyomavirus and Human Merkel Cell Carcinoma
• Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections