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Summary: Genome-scale analysis suggests that the last common ancestor of the Mycobacterium tuberculosis complex and Mycobacterium leprae diverged 36 million years ago, and members of the Mycobacterium tuberculosis complex differentiated 40 000 years ago. Analysis of palaeomicrobiological data from a 17 000-year-old sample from a bison and a 9000-year-old sample from a human being suggested that M tuberculosis preceded Mycobacterium bovis and related species. Whole-genome comparisons show that members of the M tuberculosis complex form a unique bacterial species with distinct ecotypes that are transmissible from any infected mammalian species to several others. Genomic deletions identified several M tuberculosis lineages that could be placed on a phylogeographical map, suggesting adaptation to local host populations. The degrees of transmissibility and virulence vary between M tuberculosis clones, with increased virulence mainly linked to gene loss in regulatory pathways. Such data suggest that most M tuberculosis clones have a restricted spreading capacity between the host population, allowing unpredictable bursts of highly transmissible, virulent, and successful clones, such as the east Asian (Beijing) clone. Advances in genomics have helped the development of molecular techniques for accurate identification of species and clones in the M tuberculosis complex, which is essential for tracing the source of infections. [ABSTRACT FROM AUTHOR]

Q fever is a zoonosis caused by Coxiella burnetii. Farm animals and pets are the main reservoirs of infection, and transmission to human beings is mainly accomplished through inhalation of contaminated aerosols. This illness is associated with a wide clinical spectrum, from asymptomatic or mildly symptomatic seroconversion to fatal disease. Q fever in children has been rarely reported. We reviewed published work on this topic. Seroepidemiological studies show that children are frequently exposed to C burnetii. However, children are less frequently symptomatic than adults following infection, and may have milder diseases. Using the standard diagnostic criteria, we identified 46 published paediatric cases only. Self-limited febrile illness and pneumonia were the most common manifestations of acute Q fever. Chronic disease manifested as endocarditis and osteomyelitis. A history of exposure to possible sources of infection with C burnetii in a child with a compatible infectious syndrome should prompt testing for Q fever. Studies are required to determine the spectrum of morbidity associated with Q fever during childhood. [ABSTRACT FROM AUTHOR]

The rodent-murine ectoparasite-human model of plague transmission does not correspond with historical details around plague pandemics in Europe. New analysis of ancient genomes reveal that Yersinia pestis was unable to be transmitted by rat fleas until around 4000 Before Present, which challenges the rodent-murine ectoparasite-human model of plague transmission and historical details around plague pandemics in Europe. In this Review, we summarise data regarding Y pestis transmission by human lice in the context of genomic evolution and co-transmission of other major epidemic deadly pathogens throughout human history, with the aim of broadening our view of plague transmission. Experimental models support the efficiency of human lice as plague vectors through infected faeces, which suggest that Y pestis could be a louse-borne disease, similar to Borrelia recurrentis, Rickettsia prowazekii, and Bartonella quintana. Studies have shown that louse-borne outbreaks often involve multiple pathogens, and several cases of co-transmission of Y pestis and B quintana have been reported. Furthermore, an exclusive louse-borne bacterium, namely B recurrentis, was found to be circulating in northern Europe during the second plague pandemic (14th-18th century). Current data make it possible to attribute large historical pandemics to multiple bacteria, and suggests that human lice probably played a preponderant role in the interhuman transmission of plague and pathogen co-transmission during previous large epidemics, including plague pandemics. [ABSTRACT FROM AUTHOR]

Summary: Antibiotics and probiotics are widely used as growth promoters in agriculture. Most antibiotics prescribed in clinical practice are natural products that originate from Streptomyces spp, which were first used as agricultural probiotics. Antibiotics and probiotics both modify the gut microbiota. The effect of a probiotic species on the digestive flora depends on the strain and is largely determined by bacteriocin production. In human beings, as in animals, specific probiotics are associated with weight gain or loss. Improved understanding of the ability of specific probiotics to harvest energy from the host diet might lead to development of new treatments for obesity and malnutrition. In this Review, we present the effects of probiotics and antibiotics on the gut microbiota of human beings and animals and discuss their potential therapeutic use as interventions for weight gain and loss in human beings. [ABSTRACT FROM AUTHOR]

Summary: The availability of genome sequences is revolutionising the fields of bacteriology and infectious diseases. By mid-2007, 479 bacterial genomes from 352 distinct species have been sequenced, including representatives of all notable human pathogens. Additionally, the genomes of several strains from each of 55 species have been sequenced. This tremendous amount of genomic data has led to unprecedented advances in pathogen diagnosis, genotyping, detection of virulence, and detection of resistance to antibiotics. We review current achievements in these fields and potential developments in the future for the clinical microbiology laboratory. [Copyright &y& Elsevier]

Summary: The classic epidemiological model of plague is an infection of rodents that is transmitted to human beings by rodent ectoparasites. This model fits with observations of sporadic and limited outbreaks, but hardly explains the persistence of plague foci for millennia or the epidemiological features drawn from the descriptions of historical pandemics. A comprehensive review of the published data, including scientific papers published in France between 1920 and 1940, allows the completion of the epidemiological chain by introducing soil as a reservoir, burrowing rodents as a first link, and human ectoparasites as the main driving force for pandemics. Modern studies are needed to confirm the validity of this controversial model and to assess the relative contribution of each link in the various epidemiological presentations of plague. If confirmed, these data should be taken into account to update public-health policies and bioterrorism risk management, particularly among ectoparasite-infested people. [Copyright &y& Elsevier]

The compilation of the complete prokaryotic repertoire associated with human beings as commensals or pathogens is a major goal for the scientific and medical community. The use of bacterial culture techniques remains a crucial step to describe new prokaryotic species. The large number of officially acknowledged bacterial species described since 1980 and the recent increase in the number of recognised pathogenic species have highlighted the absence of an exhaustive compilation of species isolated in human beings. By means of a thorough investigation of several large culture databases and a search of the scientific literature, we built an online database containing all human-associated prokaryotic species described, whether or not they had been validated and have standing in nomenclature. We list 2172 species that have been isolated in human beings. They were classified in 12 different phyla, mostly in the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla. Our online database is useful for both clinicians and microbiologists and forms part of the Human Microbiome Project, which aims to characterise the whole human microbiota and help improve our understanding of the human predisposition and susceptibility to infectious agents. [ABSTRACT FROM AUTHOR]

Summary: Background: Substantial reductions in malaria have been reported in several African countries after distribution of insecticide-treated bednets and the use of artemisinin-based combination therapies (ACTs). Our aim was to assess the effect of these policies on malaria morbidity, mosquito populations, and asymptomatic infections in a west African rural population. Methods: We did a longitudinal study of inhabitants of Dielmo village, Senegal, between January, 2007, and December, 2010. We monitored the inhabitants for fever during this period and we treated malaria attacks with artesunate plus amodiaquine. In July, 2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to all villagers. We did monthly night collections of mosquitoes during the whole study period, and we assessed asymptomatic carriage from cross-sectional surveys. Our statistical analyses were by negative binomial regression, logistic regression, and binomial or Fisher exact test. Findings: There were 464 clinical malaria attacks attributable to Plasmodium falciparum during 17 858 person-months of follow-up. The incidence density of malaria attacks averaged 5·45 (95% CI 4·90–6·05) per 100 person-months between January, 2007, and July, 2008, before the distribution of LLINs. Incidence density decreased to 0·41 (0·29–0·55) between August, 2008, and August, 2010, but increased back to 4·57 (3·54–5·82) between September and December, 2010—ie, 27–30 months after the distribution of LLINs. The rebound of malaria attacks were highest in adults and children aged 10 years or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%) of 384 in 2007 and 2008 (p<0·0001). 37% of Anopheles gambiae mosquitoes were resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0·0009). Interpretation: Increasing pyrethroid resistance of A gambiae and increasing susceptibility of older children and adults, probably due to decreasing immunity, caused the rebound and age shift of malaria morbidity. Strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented. Funding: Institut de Recherche pour le Développement and the Pasteur Institute of Dakar. [Copyright &y& Elsevier]

Summary: Background: Q fever endocarditis caused by Coxiella burnetii is a potentially fatal disease characterised by a chronic evolution. To assess the long-term outcome and identify prognostic factors for mortality, surgical treatment, and serological changes in Q fever endocarditis, we did a retrospective study in the French National Referral Centre. Methods: Patients included were diagnosed with Q fever endocarditis at our centre from May, 1983, to June, 2006, and followed up for a minimum of 3 years for each patient, history and clinical characteristics were recorded with a standardised questionnaire. Prognostic factors associated with death, surgery, serological cure, and serological relapse were assessed by Cox regression analysis. Excised heart valve analysis was assessed according to duration of treatment. Findings: 104 patients were identified for inclusion in the study, although one was lost to follow-up; median follow-up was 100 months (range 37–310 months). 18 months of treatment was sufficient to sterilise the valves of all the patients except three, and 2 years of treatment sterilised all valves except one. In a multivariate Cox regression analysis, the major determinants associated with mortality were age (hazard ratio 1·11, 95% CI 1·05–1·18, p=0·003), stroke at diagnosis (7·09, 2·00–25·10, p=0·001), endocarditis on a prosthetic valve (6·04, 1·47–24·80, p=0·044), an absence of a four-times decrease of phase I IgG and IgA at 1 year (5·69, 1·00–32·22, p=0·049), or the presence of phase II IgM at 1 year (12·08, 3·11–46·85, p=0·005). Surgery was associated with heart failure (2·68, 1·21–5·94, p=0·015) or a cardiac abscess (4·71, 1·64–13·50, p=0·004). The determinants of poor serological outcome were male sex (0·47, 0·26–0·86, p=0·014), a high level of phase I IgG (0·65, 0·45–0·95, p=0·027), and a delay in the start of treatment with hydroxychloroquine (0·20, 0·04–0·91, p=0·037). Factors associated with relapse were endocarditis on a prosthetic valve (21·3, 2·05–221·86, p=0·01) or treatment duration less than 18 months (9·69, 1·08–86·72, p=0·042). Interpretation: The optimum duration of treatment with doxycycline and hydroxychloroquine in Q fever endocarditis is 18 months for native valves and 24 months for prosthetic valves. This duration should be extended only in the absence of favourable serological outcomes. Patients should be serologically monitored for at least 5 years because of the risk of relapse. Funding: French National Referral Centre for Q Fever. [Copyright &y& Elsevier]

Summary: Epidemic typhus is transmitted to human beings by the body louse Pediculus humanus corporis. The disease is still considered a major threat by public-health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Until recently, Rickettsia prowazekii, the causal agent, was thought to be confined to human beings and their body lice. Since 1975, R prowazekii infection in human beings has been related to contact with the flying squirrel Glaucomys volans in the USA. Moreover, Brill-Zinsser disease, a relapsed form of epidemic typhus that appears as sporadic cases many years after the initial infection, is unrelated to louse infestation. Stress or a waning immune system are likely to reactivate this earlier persistent infection, which could be the source of new epidemics when conditions facilitate louse infestation. Finally, R prowazekii is a potential category B bioterrorism agent, because it is stable in dried louse faeces and can be transmitted through aerosols. An increased understanding of the pathogenesis of epidemic typhus may be useful for protection against this bacterial threat. [Copyright &y& Elsevier]

Summary: 100 years after its first description by George H Whipple, the diagnosis and treatment of Whipple''s disease is still a subject of controversy. Whipple''s disease is a chronic multisystemic disease. The infection is very rare, although the causative bacterium, Tropheryma whipplei, is ubiquitously present in the environment. We review the epidemiology of Whipple''s disease and the recent progress made in the understanding of its pathogenesis and the biology of its agent. The clinical features of Whipple''s disease are non-specific and sensitive diagnostic methods such as PCR with sequencing of the amplification products and immunohistochemistry to detect T whipplei are still not widely distributed. The best course of treatment is not completely defined, especially in relapsing disease, neurological manifestations, and in cases of immunoreconstitution after initiation of antibiotic treatment. Patients without the classic symptoms of gastrointestinal disease might be misdiagnosed or insufficiently treated, resulting in a potentially fatal outcome or irreversible neurological damage. Thus, we suggest procedures for the improvement of diagnosis and an optimum therapeutic strategy. [Copyright &y& Elsevier]

Summary: Resolution of infections depends on the host''s ability to mount a protective immune response. However, an exacerbated response to infections may result in deleterious lesions. Consequently, immunoregulatory mechanisms are needed to control immune response and prevent infection-associated lesions. Interleukin 10 may be a major regulator of innate and adaptive immunity in vitro and in animals, but its role in human infections is still unclear. Review of the published work reveals wide involvement of interleukin 10 in two major features of infectious diseases. On one hand, interleukin 10 prevents the development of immunopathological lesions that result from exacerbated protective immune response to acute and chronic infections. On the other hand, it is critically involved in persistence of bacteria and viruses by interfering with innate and adaptive protective immunity. Moreover, infections induce the expansion of interleukin-10-producing regulatory cells that are involved in protection against allergic diseases. [Copyright &y& Elsevier]

African tick bite fever is an acute febrile illness that is frequently accompanied by headache, prominent neck muscle myalgia, inoculation eschars, and regional lymphadenitis. The disease is caused by Rickettsia africae, a recently identified spotted fever group rickettsia, which is transmitted by ungulate ticks of the Amblyomma genus in rural sub-Saharan Africa and the French West Indies. Whereas reports on African tick bite fever in indigenous populations are scarce, the number of reported cases in travellers from Europe and elsewhere has recently increased significantly. Treatment with doxycycline is associated with rapid recovery in most patients.An immunofluorescence assay is recommended for the diagnosis but seroconversion is commonly delayed and this limits the usefulness of the test. Travellers to endemic areas should be informed of the risk of contracting African tick bite fever and be encouraged to take personal protective measures against tick bites. [Copyright &y& Elsevier]

The family Marseilleviridae is a new clade of giant viruses whose original member, marseillevirus, was described in 2009. These viruses were isolated using Acanthamoeba spp primarily from the environment. Subsequently, a close relative of marseillevirus was isolated from the faeces of a healthy young man, and others were detected in blood samples of blood donors and recipients and in a child with lymph node adenitis. In this Grand Round we describe the detection of marseillevirus by PCR, fluorescence in-situ hybridisation, direct immunofluorescence, and immunohistochemistry in the lymph node of a 30-year-old woman diagnosed with Hodgkin's lymphoma, together with IgG antibodies to marseillevirus. A link with viruses and bacteria has been reported for many lymphomas. We review the literature describing these associations, the criteria used to consider a causal association, and the underlying mechanisms of lymphomagenesis. Our observations suggest that consideration should be given to marseillevirus infections as an additional viral cause or consequence of Hodgkin's lymphoma, and that this hypothesis should be tested further. [ABSTRACT FROM AUTHOR]