Archive for the ‘Emerging disease’ Category
Maggots or MRSA?
Saturday, March 21st, 2009
Larval therapy for leg ulcers (VenUS II): randomised controlled trial. BMJ 2009;338:b773
Objective: To compare the clinical effectiveness of larval therapy with a standard debridement technique (hydrogel) for sloughy or necrotic leg ulcers.
Design: Pragmatic, three armed randomised controlled trial.
Setting: Community nurse led services, hospital wards, and hospital outpatient leg ulcer clinics in urban and rural settings, United Kingdom.
Participants: 267 patients with at least one venous or mixed venous and arterial ulcer with at least 25% coverage of slough or necrotic tissue, and an ankle brachial pressure index of 0.6 or more.
Interventions: Loose larvae, bagged larvae, and hydrogel.
Main outcome measures: The primary outcome was time to healing of the largest eligible ulcer. Secondary outcomes were time to debridement, health related quality of life (SF-12), bacterial load, presence of meticillin resistant Staphylococcus aureus, adverse events, and ulcer related pain (visual analogue scale, from 0 mm for no pain to 150 mm for worst pain imaginable).
Results: Time to healing was not significantly different between the loose or bagged larvae group and the hydrogel group (hazard ratio for healing using larvae v hydrogel 1.13, 95% confidence interval 0.76 to 1.68; P=0.54). Larval therapy significantly reduced the time to debridement (2.31, 1.65 to 3.2; P<0.001). Health related quality of life and change in bacterial load over time were not significantly different between the groups. 6.7% of participants had MRSA at baseline. No difference was found between larval therapy and hydrogel in their ability to eradicate MRSA by the end of the debridement phase (75% (9/12) v 50% (3/6); P=0.34), although this comparison was underpowered. Mean ulcer related pain scores were higher in either larvae group compared with hydrogel (mean difference in pain score: loose larvae v hydrogel 46.74 (95% confidence interval 32.44 to 61.04), P<0.001; bagged larvae v hydrogel 38.58 (23.46 to 53.70), P<0.001).
Conclusions: Larval therapy did not improve the rate of healing of sloughy or necrotic leg ulcers or reduce bacterial load compared with hydrogel but did significantly reduce the time to debridement and increase ulcer pain.
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HIV is evolving rapidly to escape the immune system
Friday, February 27th, 2009
HIV is evolving rapidly to escape the human immune system. Researchers have shown HIV is able to adapt rapidly to counter human genes controlling immune system molecules that can target it for destruction. Progression to AIDS is tied to genes which control production of key immune system molecules called human leucocyte antigens (HLAs). Humans differ in the HLA genes they have, and even small differences can have a big impact on how quickly AIDS develops. Researchers found mutations that enabled HIV effectively to neutralise the effect of a particular HLA gene were more frequent in populations with a high prevalence of that specific gene.
Adaptation of HIV-1 to human leukocyte antigen class I. Nature, 25 February 2009
The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host–pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8+ T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection1. Mutation within these epitopes can allow viral escape from CD8+ T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128–135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8+ T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.
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How mosquitoes survive dengue virus infection
Friday, February 13th, 2009
Dengue fever and dengue hemorrhagic fever are major global public health burdens, with up to 100 million cases occurring annually, yet no vaccines or specific preventative medicines are currently available. Dengue viruses, globally the most prevalent arboviruses, are transmitted to humans by persistently infected Aedes aegypti mosquitoes. However, although DENVs can cause severe disease in humans, mosquito infections are non-pathogenic and persistent. Determining how the virus evades the mosquito’s defense is an important next step in research that aims to fight disease by interrupting the growth of dengue virus within the mosquito before it can be transmitted. Researchers have discovered that mosquitoes that transmit deadly viruses such as dengue avoid becoming ill by mounting an immediate, potent immune response. Because their immune system does not eliminate the virus however, they are able to pass it on to a new victim. The researchers showed that RNA interference – a mosquito immune response – is initiated immediately after they ingest blood containing dengue virus, but the virus multiplies in the mosquitoes nevertheless.
RNA interference is an evolutionarily ancient antiviral defense used by mosquitoes and other invertebrates to destroy the RNA of many invading arthropod-borne viruses. This team of researchers previously showed that ramping up the RNA interference response in mosquitoes prevented dengue infection, and now they show that temporarily impairing this immune response increased virus transmission. The investigators analyzed RNA from adult mosquitoes, finding that both the trigger and initiator molecules for RNA interference were formed after infection, yet viral RNA could readily be detected in the same mosquitoes. They also measured infectious virus rates in the mosquitoes’ saliva, which revealed levels whereby the mosquitoes could transmit the disease to humans. These findings indicate that genetic manipulation of RNA interference could be a significant weapon in stopping dengue virus transmission by Aedes aegypti.
Understanding the mechanisms mosquitoes use to modulate infections by these agents of serious human diseases should give us critical insights into virus–vector interactions leading to transmission. RNA interference (RNAi) is an innate defense mechanism used by invertebrates to inhibit RNA virus infections; however, little is known about the antiviral role of RNAi in mosquitoes. RNAi is triggered by double-stranded RNA, leading to degradation of RNA with sequence homology to the dsRNA trigger. Dengue virus type 2 (DENV2) infection of Ae. aegypti by the natural route generates dsRNA and DENV2-specific small interfering RNAs, hallmarks of the RNAi response; nevertheless, persistent infection of mosquitoes occurs, suggesting that DENV2 circumvents RNAi. DENV2 infection is also modulated by RNAi, since impairment by silencing expression of genes encoding important sensor and effector proteins in the RNAi pathway increases virus replication in the vector and decreases the incubation period before virus transmission.
Dengue Virus Type 2 Infections of Aedes aegypti Are Modulated by the Mosquito’s RNA Interference Pathway. PLoS Pathog 5(2): e1000299
A number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (DENV) infections, but little is known about the innate immune response of the mosquito vector Aedes aegypti to arbovirus infection. We present evidence here that a major component of the mosquito innate immune response, RNA interference (RNAi), is an important modulator of mosquito infections. The RNAi response is triggered by double-stranded RNA (dsRNA), which occurs in the cytoplasm as a result of positive-sense RNA virus infection, leading to production of small interfering RNAs (siRNAs). These siRNAs are instrumental in degradation of viral mRNA with sequence homology to the dsRNA trigger and thereby inhibition of virus replication. We show that although dengue virus type 2 (DENV2) infection of Ae. aegypti cultured cells and oral infection of adult mosquitoes generated dsRNA and production of DENV2-specific siRNAs, virus replication and release of infectious virus persisted, suggesting viral circumvention of RNAi. We also show that DENV2 does not completely evade RNAi, since impairing the pathway by silencing expression of dcr2, r2d2, or ago2, genes encoding important sensor and effector proteins in the RNAi pathway, increased virus replication in the vector and decreased the extrinsic incubation period required for virus transmission. Our findings indicate a major role for RNAi as a determinant of DENV transmission by Ae. aegypti.
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Saturday Cinema: Hunting the next killer virus
Saturday, February 7th, 2009Joe DeRisi talks about amazing new ways to diagnose viruses (and treat the illnesses they cause) using DNA. His work may help us understand malaria, SARS, avian flu – and the 60 percent of everyday viral infections that go undiagnosed.
The Pathogenicity of Pandemic Influenza Viruses
Thursday, February 5th, 2009Dr. Peter Palese describes how reconstructing the extinct 1918 pandemic influenza virus by reverse genetics can help us better understand molecular basis of virulence and the mechanisms by which pandemic influenza viruses are transmitted.
UK Lassa Fever Case
Friday, January 23rd, 2009
A patient is being treated for Lassa fever at the high security infectious diseases unit at the Royal Free Hospital in London. The Health Protection Agency say this is an isolated case in a traveller who returned to the UK from Nigeria. They are trying to identify nurses and doctors at two other hospitals who cared for the man before the disease was identified. Lassa fever is spread through direct contact with body fluids.
Pathogenic soil bacterium is influenced by land management
Tuesday, January 20th, 2009
Melioidosis is a severe disease affecting humans and animals in the tropics. It is caused by the bacterium Burkholderia pseudomallei, which lives in tropical soil and especially occurs in southeast Asia and northern Australia. Despite the recognition that melioidosis is an emerging infectious disease, little is known about the habitat of B. pseudomallei in the environment.
Researchers from Menzies School of Health Research in Darwin, Australia have found that the soil bacterium Burkholderia pseudomallei, which causes the emerging infectious disease melioidosis in humans and animals, is associated with land management changes such as livestock husbandry or residential gardening. They performed a survey in the Darwin area in tropical Australia, screening 809 soil samples for the presence of these bacteria using molecular methods. The study sheds light on the environmental occurrence of this bacterium in the soil.
B. pseudomallei lives in tropical soil and is endemic in southeast Asia and northern Australia, where it can be a common cause of fatal community-acquired bacterial pneumonia. In predisposed hosts such as those with diabetes, it can also lead to systemic sepsis, with mortality rates over 50 percent. Through a large survey in the tropical Darwin area of Australia, the authors found that environmental factors describing the habitat of these bacteria differed between environmentally undisturbed and disturbed sites. At undisturbed sites, B. pseudomallei was primarily found in close proximity to streams and in grass- and roots-rich areas. In disturbed soil, B. pseudomallei was associated with the presence of animals, farming or irrigation. Highest B. pseudomallei counts were retrieved from paddocks, pens and kennels holding livestock and dogs. This study contributes to the elucidation of the habitat of B. pseudomallei in northern Australia. It also raises concerns that B. pseudomallei may spread due to changes in land management.
These findings raise concerns that B. pseudomallei may spread due to the influence of land management changes. This would increase the risk of human and livestock exposure to these potentially deadly bacteria which are transmitted by contact with contaminated soil or surface water through cuts in the skin or inhalation. In-depth analysis of the influence of anthropogenic factors upon B. pseudomallei and further studies in other endemic areas are needed to confirm the results of this study.
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Microbial diseases of bees
Thursday, January 15th, 2009
Bees are important contributors to the economies of many countries, but as Travis Glare and Maureen O’Callaghan discuss in this article in Microbiology Today, they are many threats to the survival on the humble bee, including the risk of disease from micro-organisms:
There are many threats to bee survival, including the risk of disease caused by micro-organisms. The vast majority of our knowledge of bee diseases focuses on the honey bee, Apis mellifera, although there are actually over 20,000 species, both stingless and stinging, from those with solitary lifestyles to complex societies such as honey bee hives. Viruses, fungi, protozoa and bacteria are all known to cause infections in bees, sometimes leading to collapse of colonies, and causing serious threats to the bee-keeping industry. Bees have two distinct life forms, brood (egg, larva and pupal stages which develop within the hive) and adult. Most diseases are specific to just one of these life stages. While the list of diseases is quite long, only a few are of serious concern to apiculturists.
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