382 research outputs found

    Almost sure convergence of maxima for chaotic dynamical systems

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    ArticleSuppose (f,X,ν) is a measure preserving dynamical system and ϕ:X→R is an observable with some degree of regularity. We investigate the maximum process M n :=max{X 1 ,…,X n } , where X i =ϕ∘f i is a time series of observations on the system. When M n →∞ almost surely, we establish results on the almost sure growth rate, namely the existence (or otherwise) of a sequence u n →∞ such that M n /u n →1 almost surely. The observables we consider will be functions of the distance to a distinguished point x ~ ∈X . Our results are based on the interplay between shrinking target problem estimates at x ~ and the form of the observable (in particular polynomial or logarithmic) near x ~ . We determine where such an almost sure limit exists and give examples where it does not. Our results apply to a wide class of non-uniformly hyperbolic dynamical systems, under mild assumptions on the rate of mixing, and on regularity of the invariant measure

    An outbreak of food poisoning among children attending an international sports event in Johannesburg

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    Objectives. To describe an outbreak of food poisoning at a major international sports event in Johannesburg and to determine the likely cause and source of the outbreak.Design. A descriptive, case-control study.Setting. An international sports event in Johannesburg.Methods. A questionnaire survey of involved children was used to conduct a case-control study. Microbiological and chemical analysis of the implicated food was undertaken. Site visits to the premises involved in food preparation were conducted.Results. A total of 578 children were involved. Of the 361 children who returned questionnaires, 134 were affected by an acute-onset emetic-type illness, while 53 children developed diarrhoea. Consumption of fruit juice was associated with acute illness, while diarrhoea was associated with the consumption of maize-meal porridge (pap) and chicken stew. Microbiological analysis revealed high bacterial loads in samples of the fruit juice and the presence of Shigella flexneri in the maize-meal porridge. Visits to the suppliers of the implicated foods revealed several deficiencies in terms of food hygiene precautions.Conclusion. The likely vehicles and causes of this outbreak are elucidated. Guidelines for monitoring the supply and distribution of food to future similar events should be established. Furthermore, hospitals should have protocols in place to deal with such outbreaks in a manner that facilitates epidemiological investigation

    Incidence and severity of childhood pneumonia in the first year of life in a South African birth cohort: the Drakenstein Child Health Study

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    Background Childhood pneumonia causes substantial mortality and morbidity. Accurate measurements of pneumonia incidence are scarce in low-income and middle-income countries, particularly after implementation of pneumococcal conjugate vaccine. We aimed to assess the incidence, severity, and risk factors for pneumonia in the fi rst year of life in children enrolled in a South African birth cohort. Methods This birth cohort study is being done at two sites in Paarl, a periurban area of South Africa. We enrolled pregnant women (>18 years) and followed up mother–infant pairs to 1 year of age. We obtained data for risk factors and respiratory symptoms. Children received 13-valent pneumococcal conjugate vaccine according to national immunisation schedules. We established pneumonia surveillance systems and documented episodes of ambulatory pneumonia and pneumonia warranting hospital admission. We calculated incidence rate ratios for pneumonia with mixed-eff ects Poisson regression. Findings Between May 29, 2012 and May 31, 2014, we enrolled 697 infants who accrued 513 child-years of follow-up. We recorded 141 pneumonia episodes, with an incidence of 0·27 episodes per child-year (95% CI 0·23–0·32). 32 (23%) pneumonia cases were severe pneumonia, with an incidence of 0·06 episodes per child-year (95% CI 0·04–0·08). Two (1%) of 141 pneumonia episodes led to death from pneumonia. Maternal HIV, maternal smoking, male sex, and malnutrition were associated with an increased incidence of pneumonia. Interpretation Pneumonia incidence was high in the fi rst year of life, despite a strong immunisation programme including 13-valent pneumococcal conjugate vaccine. Incidence was associated with pneumonia risk factors that are amenable to interventions. Prevention of childhood pneumonia through public health interventions to address these risk factors should be strengthened. Funding Bill & Melinda Gates Foundation, South African Thoracic Society, Federation of Infectious Diseases Societies of South Africa, and University of Cape Town

    Comparison of a real-time multiplex PCR and sequetyping assay for pneumococcal serotyping

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    BACKGROUND: Pneumococcal serotype identification is essential to monitor pneumococcal vaccine effectiveness and serotype replacement. Serotyping by conventional serological methods are costly, labour-intensive, and require significant technical expertise. We compared two different molecular methods to serotype pneumococci isolated from the nasopharynx of South African infants participating in a birth cohort study, the Drakenstein Child Health Study, in an area with high 13-valent pneumococcal conjugate vaccine (PCV13) coverage. METHODS: A real-time multiplex PCR (rmPCR) assay detecting 21 different serotypes/-groups and a sequetyping assay, based on the sequence of the wzh gene within the pneumococcal capsular locus, were compared. Forty pneumococcal control isolates, with serotypes determined by the Quellung reaction, were tested. In addition, 135 pneumococcal isolates obtained from the nasopharynx of healthy children were tested by both serotyping assays and confirmed by Quellung testing. Discordant results were further investigated by whole genome sequencing of four isolates. RESULTS: Of the 40 control isolates tested, 25 had a serotype covered by the rmPCR assay. These were all correctly serotyped/-grouped. Sequetyping PCR failed in 7/40 (18%) isolates. For the remaining isolates, sequetyping assigned the correct serotype/-group to 29/33 (88%) control isolates. Of the 132/135 (98%) nasopharyngeal pneumococcal isolates that could be typed, 69/132 (52%) and 112/132 (85%) were assigned the correct serotype/-group by rmPCR and sequetyping respectively. The serotypes of 63/132 (48%) isolates were not included in the rmPCR panel. All except three isolates (serotype 25A and 38) were theoretically amplified and differentiated into the correct serotype/-group with some strains giving ambigous results (serotype 13/20, 17F/33C, and 11A/D/1818F). Of the pneumococcal serotypes detected in this study, 69/91 (76%) were not included in the current PCV13. The most frequently identified serotypes were 11A, 13, 15B/15C, 16F and 10A. CONCLUSION: The rmPCR assay performed well for the 21 serotypes/-groups included in the assay. However, in our study setting, a large proportion of serotypes were not detected by rmPCR. The sequetyping assay performed well, but did misassign specific serotypes. It may be useful for regions where vaccine serotypes are less common, however confirmatory testing is advisable

    Longitudinal Population Dynamics of Staphylococcus aureus in the Nasopharynx During the First Year of Life

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    Background:Staphylococcus aureus colonization is a risk factor for invasive disease. Few studies have used strain genotype data to study S. aureus acquisition and carriage patterns. We investigated S. aureus nasopharyngeal carriage in infants in an intensively sampled South African birth cohort.Methods: Nasopharyngeal swabs were collected at birth and fortnightly from 137 infants through their first year of life. S. aureus was characterized by spa-typing. The incidence of S. aureus acquisition, and median carriage duration for each genotype was determined. S. aureus carriage patterns were defined by combining the carrier index (proportion of samples testing positive for S. aureus) with genotype diversity measures. Persistent or prolonged carriage were defined by a carrier index ≥0.8 or ≥0.5, respectively. Risk factors for time to acquisition of S. aureus were determined.Results: Eighty eight percent (121/137) of infants acquired S. aureus at least once. The incidence of acquisition at the species and genotype level was 1.83 and 2.8 episodes per child-year, respectively. No children had persistent carriage (defined as carrier index of >0.8). At the species level 6% had prolonged carriage, while only 2% had prolonged carriage with the same genotype. Carrier index correlated with the absolute number of spa-CCs carried by each infant (r = 0.5; 95% CI 0.35–0.62). Time to first acquisition of S. aureus was shorter in children from households with ≥5 individuals (HR 1.06, 95% CI 1.07–1.43), with S. aureus carrier mothers (HR; 1.5, 95% CI 1.2–2.47), or with a positive tuberculin skin test during the first year of life (HR; 1.81, 95% CI 0.97–3.3).Conclusion: Using measures of genotype diversity, we showed that S. aureus NP carriage is highly dynamic in infants. Prolonged carriage with a single strain occurred rarely; persistent carriage was not observed. A correlation was observed between carrier index and genotype diversity

    Modern lineages of Mycobacterium tuberculosis exhibit lineage-specific patterns of growth and cytokine induction in human monocyte-derived macrophages

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    BACKGROUND: Strains of Mycobacterium tuberculosis vary in virulence. Strains that have caused outbreaks in the United States and United Kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. There is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of M. tuberculosis . METHODS: Strains from two major modern lineages (lineage 2 [East-Asian] and lineage 4 [Euro-American]) circulating in the Western Cape in South Africa as well as a comparator modern lineage (lineage 3 [CAS/Delhi]) were identified. We assessed two virulence associated characteristics: mycobacterial growth (in liquid broth and monocyte derived macrophages) and early pro-inflammatory cytokine induction. RESULTS: In liquid culture, Lineage 4 strains grew more rapidly and reached higher plateau levels than other strains (lineage 4 vs. lineage 2 p = 0.0024; lineage 4 vs. lineage 3 p = 0.0005). Lineage 3 strains were characterized by low and early plateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains (p<0.01) with lineage 4 strains having an intermediate phenotype. Lineage 2 strains induced the lowest levels of pro-inflammatory TNF and IL-12p40 as compared to other lineages (lineage 2: median TNF 362 pg/ml, IL-12p40 91 pg/ml; lineage 3: median TNF 1818 pg/ml, IL-12p40 123 pg/ml; lineage 4: median TNF 1207 pg/ml, IL-12p40 205 pg/ml;). In contrast, lineage 4 strains induced high levels of IL-12p40 and intermediate level of TNF. Lineage 3 strains induced high levels of TNF and intermediate levels of IL-12p40. CONCLUSIONS: Strains of M. tuberculosis from the three major modern strain lineages possess distinct patterns of growth and cytokine induction. Rapid growth and immune subversion may be key characteristics to the success of these strains in different human populations

    Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study

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    Background In children admitted to hospital, rapid, accurate diagnosis of pulmonary tuberculosis with the Xpert MTB/RIF assay is possible, but no paediatric studies have been done in the primary care setting, where most children are given care, and where microbiological diagnosis is rarely available. We assessed the diagnostic accuracy of Xpert MTB/RIF in children in primary care. Methods For this prospective study, we obtained repeat induced sputum and nasopharyngeal aspirate specimens from children (<15 years) with suspected pulmonary tuberculosis at a clinic in Khayeliwtsha, Cape Town, South Africa. We compared the diagnostic accuracy of Xpert MTB/RIF with a reference standard of culture and smear microscopy on induced sputum specimens. For the main analysis, specifi city of Xpert MTB/RIF versus liquid culture, we included only children with two interpretable Xpert MTB/RIF and induced sputum culture results. Findings Between Aug 1, 2010, and July 30, 2012, we enrolled 384 children (median age 38·3 months, IQR 21·2–56·5) who had one paired induced sputum and nasopharyngeal specimen, 309 (81%) of whom had two paired specimens. Five children (1%) tested positive for tuberculosis by smear microscopy, 26 (7%) tested positive by Xpert MTB/RIF, and 30 (8%) tested positive by culture. Xpert MTB/RIF on two induced sputum specimens detected 16 of 28 culture-confi rmed cases (sensitivity of 57·1%, 95% CI 39·1–73·5) and on two nasopharyngeal aspirates detected 11 of 28 culture-confi rmed cases (sensitivity of 39·3, 23·6–57·6; p=0·18). The specifi city of Xpert MTB/RIF on induced sputum was 98·9% (95% CI 96·9–99·6) and on nasopharyngeal aspirates was 99·3% (97·4–99·8). Interpretation Our fi ndings suggest that Xpert MTB/RIF on respiratory secretions is a useful test for rapid diagnosis of paediatric pulmonary tuberculosis in primary care. Funding National Institutes of Health, National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, the National Research Foundation South Africa, the European and Developing Countries Clinical Trials Partnership

    Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays.

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    HIV-associated disseminated TB (tuberculosis) has been under-recognised and poorly characterised. Blood culture is the gold-standard diagnostic test, but is expensive, slow, and may under-diagnose TB dissemination. In a cohort of hospitalised HIV patients, we aimed to report the prevalence of TB-blood-culture positivity, performance of rapid diagnostics as diagnostic surrogates, and better characterise the clinical phenotype of disseminated TB. HIV-inpatients were systematically investigated using sputum, urine and blood testing. Overall, 132/410 (32.2%) patients had confirmed TB; 41/132 (31.1%) had a positive TB blood culture, of these 9/41 (22.0%) died within 90-days. In contrast to sputum diagnostics, urine Xpert and urine-lipoarabinomannan (LAM) combined identified 88% of TB blood-culture-positive patients, including 9/9 who died within 90-days. For confirmed-TB patients, half the variation in major clinical variables was captured on two principle components (PCs). Urine Xpert, urine LAM and TB-blood-culture positive patients clustered similarly on these axes, distinctly from patients with localised disease. Total number of positive tests from urine Xpert, urine LAM and MTB-blood-culture correlated with PCs (p < 0.001 for both). PC1&PC2 independently predicted 90-day mortality (ORs 2.6, 95%CI = 1.3-6.4; and 2.4, 95%CI = 1.3-4.5, respectively). Rather than being a non-specific diagnosis, disseminated TB is a distinct, life-threatening condition, which can be diagnosed using rapid urine-based tests, and warrants specific interventional trials
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