Tuberculosis in a South African prison – a transmission modelling analysis

Background. Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a   mathematical model was developed to explore the interactions between incarceration conditions and TB control measures.Methods. Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and  international minimum standards for incarceration.Results. Levels of overcrowding (230%) in communal cells and poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy  recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively.Conclusions. Current  conditions of detention for awaiting trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently.S Afr Med J 2011;101:809-813

Tuberculosis in a South African prison - a transmission modelling analysis

Background. Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A. recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. Methods. Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. Results. Levels of overcrowding (230%) in communal cells and Poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. Conclusions. Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently

Autologous whole ram seminal plasma and its vesicle-free fraction improve motility characteristics and membrane status but not in vivo fertility of frozen-thawed ram spermatozoa

Motility characteristics (assessed subjectively and with computer-assisted semen analysis) and membrane status (after staining with chlortetracycline) of washed and non-washed frozen-thawed ram spermatozoa were evaluated after incubation in buffer and buffer containing autologous whole seminal plasma or one of its two fractions: the pellet of membrane vesicles obtained by ultracentrifugation (and used at three times normal protein concentration) or the vesicle-free supernatant fraction. Whole seminal plasma and supernatant, but not membrane vesicles, improved the motility characteristics of spermatozoa after 3 and 6 h of post-thaw incubation compared with the control buffer. Resuspension and incubation with whole seminal plasma, supernatant or membrane vesicles lowered the proportion of acrosome-reacted frozen-thawed spermatozoa compared with the control buffer. Unwashed frozen-thawed semen from three rams, incubated with autologous whole seminal plasma or its fractions and inseminated using cervical or intrauterine artificial insemination, had no effect on pregnancy rates of ewes in synchronized oestrus. However, fertility was higher after laparoscopic than cervical insemination (44.9 vs 12.3%, p < 0.001). In conclusion, resuspension and incubation of frozen-thawed ram spermatozoa in autologous whole seminal plasma or its vesicle-free supernatant fraction improved their motility characteristics and, with membrane vesicles, membrane status, but these benefits were not reflected in improved fertility after cervical or intrauterine insemination. © 2007 The Authors

An isolate of human immunodeficiency virus type 1 originally classified as subtype I represents a complex mosaic comprising three different group M subtypes (A, G, and I)

Full-length reference clones and sequences are currently available for eight human immunodeficiency virus type 1 (HIV-1) group M subtypes (A through H), but none have been reported for subtypes I and J, which have only been identified in a few individuals. Phylogenetic information for subtype I, in particular, is limited since only about 400 bp of env gene sequences have been determined for just two epidemiologically linked viruses infecting a couple who were heterosexual intravenous drug users from Cyprus. To characterize subtype I in greater detail, we employed long-range PCR to clone a full-length provirus (94CY032.3) from an isolate obtained from one of the individuals originally reported to be infected with this subtype. Phylogenetic analysis of C2-V3 env gene sequences confirmed that 94CY032.3 was closely related to sequences previously classified as subtype I. However, analysis of the remainder of its genome revealed various regions in which 94CY032.3 was significantly clustered with either subtype A or subtype G. Only sequences located in vpr and nef, as well as the middle portions of pol and env, formed independent lineages roughly equidistant from all other known subtypes. Since these latter regions most likely have a common origin, we classify them all as subtype I. These results thus indicate that the originally reported prototypic subtype I isolate 94CY032 represents a triple recombinant (A/G/I) with at least 11 points of recombination crossover. We also screened HIV-1 recombinants with regions of uncertain subtype assignment for the presence of subtype I sequences. This analysis revealed that two of the earliest mosaics from Africa, Z321B (A/G/?) and MAL (A/D/?), contain short segments of sequence which clustered closely with the subtype I domains of 94CY032.3. Since Z321 was isolated in 1976, subtype I as well as subtypes A and G must have existed in Central Africa prior to that date... (D'après résumé d'auteur

Electron ionization mass spectral fragmentation study of sulfation derivatives of polychlorinated biphenyls

<p>Abstract</p> <p>Background</p> <p>Polychlorinated biphenyls are persistent organic pollutants that can be metabolized via hydroxylated PCBs to PCB sulfate metabolites. The sensitive and selective analysis of PCB sulfate monoesters by gas chromatography-mass spectrometry (GC-MS) requires their derivatization, for example, as PCB 2,2,2-trichloroethyl (TCE) sulfate monoesters. To aid in the identification of unknown PCB sulfate metabolites isolated from biological samples, the electron impact MS fragmentation pathways of selected PCB TCE sulfate diesters were analyzed and compared to the fragmentation pathways of the corresponding methoxylated PCBs.</p> <p>Results</p> <p>The most abundant and characteristic fragment ions of PCB TCE sulfate diesters were formed by releasing CHCCl₃, SO₃, HCl₂and/or CCl₃from the TCE sulfate moiety and Cl₂, HCl, ethyne and chloroethyne from an intermediate phenylcyclopentadienyl cation. The fragmentation pattern depended on the degree of chlorination and the position of the TCE sulfate moiety (i.e., <it>ortho </it>vs. <it>meta/para </it>to the second phenyl ring), but were independent of the chlorine substitution pattern. These fragmentation pathways are similar to the fragmentation pathways of structurally related methoxylated PCBs.</p> <p>Conclusion</p> <p>Knowledge of the fragmentation patterns of PCB TCE sulfate diesters will greatly aid in determining the position of sulfate moiety (<it>ortho </it>vs. <it>meta/para</it>) of unknown PCB sulfate metabolites isolated from environmental or laboratory samples.</p

Transient disruption of M1 during response planning impairs subsequent offline consolidation

Transcranial magnetic stimulation (TMS) was used to probe the involvement of the left primary motor cortex (M1) in the consolidation of a sequencing skill. In particular we asked: (1) if M1 is involved in consolidation of planning processes prior to response execution (2) whether movement preparation and movement execution can undergo consolidation independently and (3) whether sequence consolidation can occur in a stimulus specific manner. TMS was applied to left M1 while subjects prepared left hand sequential finger responses for three different movement sequences, presented in an interleaved fashion. Subjects also trained on three control sequences, where no TMS was applied. Disruption of subsequent consolidation was observed, but only for sequences where subjects had been exposed to TMS during training. Further, reduced consolidation was only observed for movement preparation, not movement execution. We conclude that left M1 is causally involved in the consolidation of effective response planning for left hand movements prior to response execution, and mediates consolidation in a sequence specific manner. These results provide important new insights into the role of M1 in sequential memory consolidation and sequence response planning

Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis

BACKGROUND: Rheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever. METHODS: Trials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966–2003), EMBASE (1966–2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever. RESULTS: Ten trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21–0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11–0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately US$46 in South Africa. CONCLUSION: Antibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered

Classification of HIV-1 Sequences Using Profile Hidden Markov Models

Accurate classification of HIV-1 subtypes is essential for studying the dynamic spatial distribution pattern of HIV-1 subtypes and also for developing effective methods of treatment that can be targeted to attack specific subtypes. We propose a classification method based on profile Hidden Markov Model that can accurately identify an unknown strain. We show that a standard method that relies on the construction of a positive training set only, to capture unique features associated with a particular subtype, can accurately classify sequences belonging to all subtypes except B and D. We point out the drawbacks of the standard method; namely, an arbitrary choice of threshold to distinguish between true positives and true negatives, and the inability to discriminate between closely related subtypes. We then propose an improved classification method based on construction of a positive as well as a negative training set to improve discriminating ability between closely related subtypes like B and D. Finally, we show how the improved method can be used to accurately determine the subtype composition of Common Recombinant Forms of the virus that are made up of two or more subtypes. Our method provides a simple and highly accurate alternative to other classification methods and will be useful in accurately annotating newly sequenced HIV-1 strains

Genotype by environment interaction for 450-day weight of Nelore cattle analyzed by reaction norm models

Genotype by environment interactions (GEI) have attracted increasing attention in tropical breeding programs because of the variety of production systems involved. In this work, we assessed GEI in 450-day adjusted weight (W450) Nelore cattle from 366 Brazilian herds by comparing traditional univariate single-environment model analysis (UM) and random regression first order reaction norm models for six environmental variables: standard deviations of herd-year (RRMw) and herd-year-season-management (RRMw-m) groups for mean W450, standard deviations of herd-year (RRMg) and herd-year-season-management (RRMg-m) groups adjusted for 365-450 days weight gain (G450) averages, and two iterative algorithms using herd-year-season-management group solution estimates from a first RRMw-m and RRMg-m analysis (RRMITw-m and RRMITg-m, respectively). The RRM results showed similar tendencies in the variance components and heritability estimates along environmental gradient. Some of the variation among RRM estimates may have been related to the precision of the predictor and to correlations between environmental variables and the likely components of the weight trait. GEI, which was assessed by estimating the genetic correlation surfaces, had values < 0.5 between extreme environments in all models. Regression analyses showed that the correlation between the expected progeny differences for UM and the corresponding differences estimated by RRM was higher in intermediate and favorable environments than in unfavorable environments (p < 0.0001)