Clinical manifestations of human brucellosis : a systematic review and meta-analysis

BACKGROUND: The objectives of this systematic review, commissioned by WHO, were to assess the frequency and severity of clinical manifestations of human brucellosis, in view of specifying a disability weight for a DALY calculation. METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, with 2,385 articles published between January 1990-June 2010 identified as relating to human brucellosis. Fifty-seven studies were of sufficient quality for data extraction. Pooled proportions of cases with specific clinical manifestations were stratified by age category and sex and analysed using generalized linear mixed models. Data relating to duration of illness and risk factors were also extracted. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from epididymo-orchitis. Debilitating conditions such as arthralgia, myalgia and back pain affected around half of the patients (65%, 47% and 45%, respectively). Given that 78% patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas. Significant delays in appropriate diagnosis and treatment were the result of health service inadequacies and socioeconomic factors. Based on disability weights from the 2004 Global Burden of Disease Study, a disability weight of 0.150 is proposed as the first informed estimate for chronic, localised brucellosis and 0.190 for acute brucellosis. CONCLUSIONS: This systematic review adds to the understanding of the global burden of brucellosis, one of the most common zoonoses worldwide. The severe, debilitating, and chronic impact of brucellosis is highlighted. Well designed epidemiological studies from regions lacking in data would allow a more complete understanding of the clinical manifestations of disease and exposure risks, and provide further evidence for policy-makers. As this is the first informed estimate of a disability weight for brucellosis, there need for further debate amongst brucellosis experts and a consensus to be reache

Back-calculating the incidence of infection of leprosy in a Bayesian framework

Background: The number of new leprosy cases reported annually is falling worldwide, but remains relatively high in some populations. Because of the long and variable periods between infection, onset of disease, and diagnosis, the recently detected cases are a reflection of infection many years earlier. Estimation of the numbers of sub-clinical and clinical infections would be useful for management of elimination programmes. Back-calculation is a methodology that could provide estimates of prevalence of undiagnosed infections, future diagnoses and the effectiveness of control. Methods: A basic back-calculation model to investigate the infection dynamics of leprosy has been developed using Markov Chain Monte Carlo in a Bayesian context. The incidence of infection and the detection delay both vary with calendar time. Public data from Thailand are used to demonstrate the results that are obtained as the incidence of diagnosed cases falls. Results: The results show that the underlying burden of infection and short-term future predictions of cases can be estimated with a simple model. The downward trend in new leprosy cases in Thailand is expected to continue. In 2015 the predicted total number of undiagnosed sub-clinical and clinical infections is 1,168 (846–1,546) of which 466 (381–563) are expected to be clinical infections. Conclusions: Bayesian back-calculation has great potential to provide estimates of numbers of individuals in health/infection states that are as yet unobserved. Predictions of future cases provides a quantitative measure of understanding for programme managers and evaluators. We will continue to develop the approach, and suggest that it might be useful for other NTD in which incidence of diagnosis is not an immediate measure of infection

Back-calculating the incidence of infection of leprosy in a Bayesian framework.

BACKGROUND: The number of new leprosy cases reported annually is falling worldwide, but remains relatively high in some populations. Because of the long and variable periods between infection, onset of disease, and diagnosis, the recently detected cases are a reflection of infection many years earlier. Estimation of the numbers of sub-clinical and clinical infections would be useful for management of elimination programmes. Back-calculation is a methodology that could provide estimates of prevalence of undiagnosed infections, future diagnoses and the effectiveness of control. METHODS: A basic back-calculation model to investigate the infection dynamics of leprosy has been developed using Markov Chain Monte Carlo in a Bayesian context. The incidence of infection and the detection delay both vary with calendar time. Public data from Thailand are used to demonstrate the results that are obtained as the incidence of diagnosed cases falls. RESULTS: The results show that the underlying burden of infection and short-term future predictions of cases can be estimated with a simple model. The downward trend in new leprosy cases in Thailand is expected to continue. In 2015 the predicted total number of undiagnosed sub-clinical and clinical infections is 1,168 (846-1,546) of which 466 (381-563) are expected to be clinical infections. CONCLUSIONS: Bayesian back-calculation has great potential to provide estimates of numbers of individuals in health/infection states that are as yet unobserved. Predictions of future cases provides a quantitative measure of understanding for programme managers and evaluators. We will continue to develop the approach, and suggest that it might be useful for other NTD in which incidence of diagnosis is not an immediate measure of infection

Heritability of phenotypic udder traits to improve resilience to mastitis in Texel ewes

There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h2) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis

Longitudinal Combustion Instabilities in Ramjet Engines: Identification of Acoustic Modes

Longitudinal combustion instabilities in liquid-fueled ramjet engines have been investigated with attention focused on determination of the acoustic mode structures. Detailed pressure measurements, including both amplitude and phase, were made at ten positions spanning the length of the engine. The experimental data have been analyzed using two linear acoustic models. Four distinct modes were observed for various inlet/combustor combinations. These results help identify the mechanisms exciting low-frequency pressure oscillations in ramjet engines

Biogeography of bacterioplankton in lakes and streams of an arctic tundra catchment

Author Posting. © Ecological Society of America, 2007. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Ecology 88 (2007): 1365–1378, doi:10.1890/06-0387Bacterioplankton community composition was compared across 10 lakes and 14 streams within the catchment of Toolik Lake, a tundra lake in Arctic Alaska, during seven surveys conducted over three years using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified rDNA. Bacterioplankton communities in streams draining tundra were very different than those in streams draining lakes. Communities in streams draining lakes were similar to communities in lakes. In a connected series of lakes and streams, the stream communities changed with distance from the upstream lake and with changes in water chemistry, suggesting inoculation and dilution with bacteria from soil waters or hyporheic zones. In the same system, lakes shared similar bacterioplankton communities (78% similar) that shifted gradually down the catchment. In contrast, unconnected lakes contained somewhat different communities (67% similar). We found evidence that dispersal influences bacterioplankton communities via advection and dilution (mass effects) in streams, and via inoculation and subsequent growth in lakes. The spatial pattern of bacterioplankton community composition was strongly influenced by interactions among soil water, stream, and lake environments. Our results reveal large differences in lake-specific and stream-specific bacterial community composition over restricted spatial scales (<10 km) and suggest that geographic distance and connectivity influence the distribution of bacterioplankton communities across a landscape.This research was supported in part by the University of Michigan and University of Maryland, and by National Science Foundation grants OPP-0408371, OPP-9911681, OPP- 9911278, DEB-0423385, DEB-9810222, and ATM-0423385

Antioxidant Treatment Regulates the Humoral Immune Response during Acute Viral Infection

Generation of reactive oxygen intermediates (ROI) following antigen receptor ligation is critical to promote cellular responses. However, the effect of antioxidant treatment on humoral immunity during a viral infection was unknown. Mice were infected with lymphocytic choriomeningitis virus (LCMV) and treated with Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide dismutase mimetic, from days 0 to 8 postinfection. On day 8, at the peak of the splenic response in vehicle-treated mice, virus-specific IgM and IgG antibody-secreting cells (ASC) were decreased 22- and 457-fold in MnTBAP-treated animals. By day 38, LCMV-specific IgG ASC were decreased 5-fold in the bone marrow of drug-treated mice, and virus-specific antibodies were of lower affinity. Interestingly, antioxidant treatment had no effect on the number of LCMV-specific IgG memory B cells. In addition to decreases in ASC, MnTBAP treatment decreased the number of functional virus-specific CD4+ T cells. The decreased numbers of ASC observed on day 8 in drug-treated mice were due to a combination of Bim-mediated cell death and decreased proliferation. Together, these data demonstrate that ROI regulate antiviral ASC expansion and have important implications for understanding the effects of antioxidants on humoral immunity during infection and immunization