MicrobiologyBytes

The current UK National Framework for Pandemic Influenza states that during a pandemic, domestic travel should continue to operate normally but users should adopt good hygiene measures, stagger journeys where possible to reduce overcrowding; and stay at home altogether if symptomatic with pandemic influenza. This advice reflects the need to maintain, as far as possible, business continuity and near normal functioning of society, but acknowledges that some data exist about the transmission of influenza on board public transport, notably commercial airliners. Until very recently, there were no data that directly supported or refuted an association between the use of public ground transportation and the risk of acute respiratory infection. The risk posed by large numbers of transient casual human contacts has not been adequately defined. The current uncertainty makes the formulation of pandemic transport policies difficult. So what’s the risk?

Is public transport a risk factor for acute respiratory infection? BMC Infectious Diseases 2011, 11:16doi:10.1186/1471-2334-11-16
Background: The relationship between public transport use and acquisition of acute respiratory infection (ARI) is not well understood but potentially important during epidemics and pandemics.
Methods: A case-control study performed during the 2008/09 influenza season. Cases (n=72) consulted a General Practitioner with ARI, and controls with another non-respiratory acute condition (n=66). Data were obtained on bus or tram usage in the five days preceding illness onset (cases) or the five days before consultation (controls) alongside demographic details. Multiple logistic regression modelling was used to investigate the association between bus or tram use and ARI, adjusting for potential confounders.
Results: Recent bus or tram use within five days of symptom onset was associated with an almost six-fold increased risk of consulting for ARI (adjusted OR=5.94 95% CI 1.33-26.5). The risk of ARI appeared to be modified according to the degree of habitual bus and tram use, but this was not statistically significant (1-3 times/week: adjusted OR=0.54 (95% CI 0.15-1.95; >3 times/week: 0.37 (95% CI 0.13-1.06).
Conclusions: We found a statistically significant association between ARI and bus or tram use in the five days before symptom onset. The risk appeared greatest among occasional bus or tram users, but this trend was not statistically significant. However, these data are plausible in relation to the greater likelihood of developing protective antibodies to common respiratory viruses if repeatedly exposed. The findings have differing implications for the control of seasonal acute respiratory infections and for pandemic influenza.

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This article reviews recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates. RVFV continues to extend its range in Africa and the Middle East. Better definition of RVFV-related clinical syndromes and human risk factors for severe disease, combined with early-warning systems based on remote-sensing, simplified rapid diagnostics, and tele-epidemiology, hold promise for earlier deployment of effective outbreak control measures. Advances in understanding of viral replication pathways and host cell-related pathogenesis suggest means for antiviral therapeutics and for more effective vaccination strategies based on genetically engineered virus strains or subunit vaccines. RVFV is a significant health and economic burden in many areas of Africa, and remains a serious threat to other parts of the world. Development of more effective methods for RVFV outbreak prevention and control remains a global health priority.

Advances in Rift Valley fever research: insights for disease prevention. Curr Opin Infect Dis. Jul 6 2010 doi: 10.1097/QCO.0b013e32833c3da6

Staphylococcus aureus is an invasive human pathogen with increasing incidence and morbidity in hospitals and the community. Both healthy persons and those with underlying illness are at risk for diverse skin and soft tissue infections, endocarditis, osteomyelitis, meningitis, bacteremia, and pneumonia (including pneumonia arising as a complication of influenza), with mortality rates ranging from 6–40%. The high frequency of poorly responsive and recurrent S. aureus disease in apparently immunocompetent hosts is a challenging feature of these infections. Groups that are particularly susceptible include children in daycare, sports teams, jailed inmates and military personnel. Moreover, the emergence and rapid spread of methicillin-resistant S. aureus (MRSA) has placed substantial burden on the healthcare system.

Colonization of the nares (nostrils) is a potent and increasingly prevalent risk factor for subsequent S. aureus infection. In at least 80% of S. aureus bacteremia cases in colonized subjects, the infecting strain is identical to a nasal colonizing strain detected prior to onset of bacteremia. Followed longitudinally, approximately 20–30% of persons are colonized persistently with S. aureus, 30% are colonized intermittently, and 50% never, or rarely, are colonized. Why some individuals apparently are resistant to colonization, and thus at lower risk of infection, remains an open question. Understanding the biology of this pathogen, especially its ecological niche in humans and the initial step in infection, colonization, may therefore provide new methods of limiting disease.

The Human Nasal Microbiota and Staphylococcus aureus Carriage. 2010 PLoS ONE 5(5): e10598. doi:10.1371/journal.pone.0010598
Nasal specimens were collected longitudinally from five healthy adults and a cross-section of hospitalized patients (26 S. aureus carriers and 16 non-carriers). Culture-independent analysis of 16S rRNA sequences revealed that the nasal microbiota of healthy subjects consists primarily of members of the phylum Actinobacteria (e.g., Propionibacterium spp. and Corynebacterium spp.), with proportionally less representation of other phyla, including Firmicutes (e.g., Staphylococcus spp.) and Proteobacteria (e.g. Enterobacter spp). In contrast, inpatient nasal microbiotas were enriched in S. aureus or Staphylococcus epidermidis and diminished in several actinobacterial groups, most notably Propionibacterium acnes. Moreover, within the inpatient population S. aureus colonization was negatively correlated with the abundances of several microbial groups, including S. epidermidis. The nares environment is colonized by a temporally stable microbiota that is distinct from other regions of the integument. Negative association between S. aureus, S. epidermidis, and other groups suggests microbial competition during colonization of the nares, a finding that could be exploited to limit S. aureus colonization.

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In most countries, tuberculosis (TB) notification is twice as high in men as in women. Although there is clear evidence that socioeconomic and cultural factors leading to barriers in accessing health care may cause undernotification in women, particularly in developing countries, biological mechanisms may actually account for a significant part of this difference between male and female susceptibility to TB. The role of biological gender has been determined in a number of infectious and noninfectious diseases. However, there is an absence of information on the role of biological gender in TB. Thus, investigations should be conducted to clearly understand the role of sexual hormones, sex-related genetic background and genetic regulations, and metabolism, among other factors, in susceptibility differences between men and women. This research may help not only to fully understand the obviously biased gender distribution among TB cases, but also to better adapt future intervention strategies at the community level. In this review, we expand on the various issues relating to TB notification and gender bias.

Large prevalence surveys have suggested that the sex bias observed in pulmonary TB cases may result partly from genuine biological differences in male and female susceptibility to M. tuberculosis infection or the development of TB disease. This finding would not be particularly surprising, as many studies in humans and experimentally infected animals have established clear links between sex-specific factors, including steroid hormones and genetic variants, and the differential susceptibility of males and females to a number of other infectious and noninfectious diseases. In particular, gender bias among pulmonary microbial diseases is not restricted to TB, and important sex differences in the incidence and severity of a number of respiratory tract bacterial infections have been reported in the literature. As a selected example, it has been shown that men have a four-times higher risk of developing nosocomial Legionella pneumophila infection than women. Only 5% to 10% of individuals exposed to M. tuberculosis develop TB, and up to 70% of those who do develop the disease are male. In other words, the human population as a whole is remarkably resistant to M. tuberculosis, but women seem to be even more resistant to the bacillus than men. So, why do only a minority of individuals, other than patients with HIV/AIDS, fail to control infection? Why are women less likely to develop TB than men? Why are some women more resistant to TB than other women exposed to a similar extent? Field research consortia including not only microbiologists, immunologists, and human geneticists, but also epidemiologists and sociologists, should be established to unravel the many faces of sexual inequality in TB, and to decipher the delicate mechanisms involved in natural and sex-associated resistance to TB. Such work would facilitate the design of future intervention strategies for combating the disease and the development of useful tools for evaluating prognosis and protection in future clinical trials.

Sexual Inequality in Tuberculosis. PLoS Med 6(12): e1000199. doi:10.1371/journal.pmed.1000199

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Research published this week in PLoS Medicine presents the most accurate assessment to date of the severity of the swine flu (H1N1) pandemic in the US. Scientists need to measure the severity of swine flu (how often infection with the swine flu virus results in symptoms leading to illness, hospitalization or death) so that appropriate pandemic plans can be put into place. Severity of swine flu has been difficult to measure for two main reasons: first, people with severe influenza are more likely than those with mild cases to seek care, making it difficult to estimate how many total cases have occurred, and second, the sheer number of cases means that recording routine case data can be difficult due to overburdening of public health systems. In this study, researchers from from Milwaukee (where all medically attended cases were recorded, whether hospitalized or not) and New York City (where only hospitalizations, intensive care admission and deaths were recorded, and a telephone survey of flu-like illness was conducted), along with earlier results from studies by the US CDC, used a statistical approach called Bayesian evidence synthesis. This enabled accurate estimations of severity to be made. Their analyses reveal that the autumn-winter pandemic wave of swine flu should have a death toll only slightly higher than, or considerably lower than, that caused by seasonal influenza in an average year, provided swine flu continues to behave as it did during the summer. Seasonal influenza mainly kills elderly adults, but the authors reveal that most deaths from swine flu will occur in non-elderly adults, a shift in age distribution that has been seen in previous pandemics.

The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A bayesian Analysis. PLoS Med 6(12): e1000207 doi:10.1371/journal.pmed.1000207
Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data – medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York – were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%–0.096%), sCIR of 0.239% (0.134%–0.458%), and sCHR of 1.44% (0.83%–2.64%). Using self-reported ILI, we obtained estimates approximately 7–96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5–17 y. sCHR appears to be lowest in persons aged 5–17; our data were too sparse to allow us to determine the group in which it was the highest. These estimates suggest that an autumn–winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0–4 and adults 18–64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.

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Wild waterfowl and seabirds are major natural reservoirs of influenza A viruses. Genetic analysis has revealed that influenza A viruses found in all other host species, including humans, were ultimately derived from avian viruses. Geographical separation of host species has shaped the influenza gene pool into largely independently evolving Eurasian and American lineages, although some gene flow between these regions has been documented.

Reassortment between Eurasian and North American lineage viruses have also been documented in wild aquatic bird populations indicating that in these two geographically segregated lineages there is some mixing of viruses. However, the possible effects of virus gene flow between the Eurasian and American gene pools on influenza virus evolution and population structure had not been fully explored until recently. A new study shows that virus gene flow from Eurasia has led to the exclusion of some viruses from North America, most likely mediated by competition for susceptible hosts (Gene flow and competitive exclusion of avian influenza A virus in natural reservoir hosts. Virology, 5 June 2009 doi:10.1016/j.virol.2009.05.002).

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The researchers found that intercontinental gene flow is frequently mediated through seabirds, highlighting the need for increased surveillance of influenza viruses in a broader spectrum of potential host species. Such selection is only likely to occur in cases where the viruses in question are sufficiently antigenically similar to induce a cross-protective immune response.

Population genetics offers a number of concepts and principles to explain the evolutionary behavior of RNA viruses. For example, the competitive exclusion principle states that when two species compete for limited resources one species will eventually outcompete the other and become dominant. In the case of RNA viruses, a combination of high replication numbers and high nucleotide substitution rates makes the prolonged co-existence of two or more genetically distinct virus populations unlikely. In theory, the competitive pressure exerted by an invading influenza virus will select for viruses with increased reproduction and transmissibility. Therefore the adaptive advantage conferred through competition may contribute to influenza disease emergence.

Increased genome surveillance of influenza viruses in bird populations is critical for understanding the effects of gene flow between populations. The extent of virus competition in avian populations infected with influenza remains unknown. In Asia, the long-term endemicity of H5N1 influenza appears to have replaced, most probably through competitive selection, low pathogenic H5 subtype viruses that have been only rarely isolated from poultry in Asia since 2000 when compared to previous surveillance in the 1970′s. This new work provides a possible mechanism for disease emergence and transmission from natural reservoir hosts.

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