Browsing by Subject "Pneumonia"
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- ItemOpen AccessThe anti-Pseudomonas aeruginosa antibody Panobacumab is efficacious on acute pneumonia in neutropenic mice and has additive effects with meropenem(Public Library of Science, 2013) Secher, Thomas; Fas, Stefanie; Fauconnier, Louis; Mathieu, Marieke; Rutschi, Oliver; Ryffel, Bernhard; Rudolf, MichaelPseudomonas aeruginosa ( P. aeruginosa ) infections are associated with considerable morbidity and mortality in immunocompromised patients due to antibiotic resistance. Therefore, we investigated the efficacy of the anti- P. aeruginosa serotype O11 lipopolysaccharide monoclonal antibody Panobacumab in a clinically relevant murine model of neutropenia induced by cyclophosphamide and in combination with meropenem in susceptible and meropenem resistant P. aeruginosa induced pneumonia. We observed that P. aeruginosa induced pneumonia was dramatically increased in neutropenic mice compared to immunocompetent mice. First, Panobacumab significantly reduced lung inflammation and enhanced bacterial clearance from the lung of neutropenic host. Secondly, combination of Panobacumab and meropenem had an additive effect. Third, Panobacumab retained activity on a meropenem resistant P. aeruginosa strain. In conclusion, the present data established that Panobacumab contributes to the clearance of P. aeruginosa in neutropenic hosts as well as in combination with antibiotics in immunocompetent hosts. This suggests beneficial effects of co-treatment even in immunocompromised individuals, suffering most of the morbidity and mortality of P. aeruginosa infections.
- ItemOpen AccessApplications of aspiration lung biopsy with special reference to the pathogenesis of the resolution of acute and chronic lobar pneumonia(1951) Woolf, Colin Rael; Forman, F; Landau, ALung biopsy is neither widely known nor practiced and it was only in 1949 that i first came across a paper on this subject. The title was: "Cellular analysis of the aspiration lung biopsy from normal and some pathological conditions by Z. Godlowski" (1949). The very term "lung biopsy" conjures up the picture of a needle being introduced into an air filled, very vascular structure where the bleeding of an injured vessel cannot readily be stopped, where the stage is set for air embolisms and where tension pneumothorax may occur. it was with great surprise but also an apparently innocuous procedure. Unfortunately, at that time, there was no opportunity to use the method. In 1950 I became the University Assistant at the New Somerset Hospital in Cape Town. Many of the cases admitted to the wards presented with chest pathology. Patients with pneumococcal lobar pneumonia were not infrequent and occasional cases did not resolve as expected but went on to become so-called chronic pneumonia. What happened when an acute lobar pneumonia went on to the chronic stage and why did this occur? it was suggested that investigae this problem.
- ItemOpen AccessBacterial disease and antimicrobial susceptibility patterns in HIV-infected, hospitalized children: a retrospective cohort study(Public Library of Science, 2008) Jaspan, Heather B; Huang, Lyen C; Cotton, Mark F; Whitelaw, Andrew; Myer, LandonBACKGROUND: Serious bacterial infections are a major source of morbidity and mortality in HIV-infected children. The spectrum of disease is wide, and responsible organisms vary according to setting. The use of antibiotic prophylaxis and the emergence of multi-drug resistant bacteria necessitate examination of responsible organisms and their antibiotic susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study of all HIV-positive pediatric admissions at an urban public sector hospital in Cape Town between January 2002 and June 2006 was conducted. Children between the ages of one month and nine years with laboratory confirmed HIV status, serious bacterial infection, and a hospital length of stay of 5 days or more, were eligible for inclusion. Organisms isolated from blood, urine, and cerebral spinal fluid cultures and their antimicrobial susceptibility were examined, and compared according to timing of isolation to distinguish nosocomial versus community-acquired. One hundred and forty-one children were identified (median age 1.2 years), 39% of whom were on antiretrovirals started before or during this hospitalization. Bacterial infections involved all organ systems, however pneumonia was most common (67%). S. pneumoniae and S. aureus were the most common gram positive and K. pneumoniae was the most common gram negative organism. K pneumoniae isolates were resistant to many first and second line antibiotics, and were all considered nosocomial. All S. aureus isolates were methicillin resistant, some of which were community-acquired. Conclusions/Significance Bacterial infections are an important source of co-morbidity in HIV-infected children in resource-limited settings. Clinicians should have a low threshold to initiate antibiotics in children requiring hospitalization. Broad-spectrum antibiotics should be used judiciously. Clinicians caring for HIV-infected children should be cognizant of the most common organisms affecting such children, and of their local antimicrobial susceptibilities, when treating empirically for serious bacterial infections.
- ItemOpen AccessDetection of Streptococcus pneumoniae from different types of nasopharyngeal swabs in children(Public Library of Science, 2013) Dube, Felix S; Kaba, Mamadou; Whittaker, Elizabeth; Zar, Heather J; Nicol, Mark PBACKGROUND: A better understanding of the epidemiology of nasopharyngeal carriage of Streptococcus pneumoniae is important to assess the impact of vaccination and the pathogenesis of pneumococcal disease. We compared the recovery of S. pneumoniae from nylon flocked, Dacron and rayon swabs. METHODS: The recovery of S. pneumoniae from mocked specimens using flocked, Dacron and rayon swabs were compared by culture. The yield from paired nasopharyngeal (NP) samples obtained from healthy children sampled with flocked and Dacron swabs was also determined using culture and lytA -targeted real-time polymerase chain reaction (qPCR). RESULTS: Using mock specimen, the percentage recovery of S. pneumoniae ATCC 49619 (serotype 19F) strain from the flocked swabs was 100%, while it was 41% from Dacron swabs and 7% from rayon swabs. Similar results were observed for S. pneumoniae serotypes 1 and 5. S. pneumoniae was cultured from 18 of 42 (43%) paired NP samples from the healthy children (median age 8 [interquartile range (IQR) 5-16] months). The median number of colony-forming units (CFU) recovered from flocked swabs was two-fold higher (8.8×10 4 CFU/mL [IQR, 2.0×10 2 - 4.0×10 5 CFU/mL]) than Dacron swabs (3.7×10 4 CFU/mL [IQR, 4.0×10 2 -3.2×10 5 CFU/mL], p = 0.17). Using lytA -targeted qPCR from paired NP samples, the median copy number of S. pneumoniae detected from flocked swabs was significantly higher than from Dacron swabs (3.0×10 5 genome copies/mL [IQR, 1.3×10 2 −1.8×10 6 ] vs. 9.3×10 4 genome copies/mL [IQR, 7.0×10 1 −1.1×10 6 ]; p = 0.005). CONCLUSION: Flocked swabs released more S. pneumoniae compared to both Dacron and rayon swabs from mock specimens. Similarly, higher bacterial loads were detected by qPCR from flocked swabs compared with Dacron swabs from healthy children.
- ItemOpen AccessHand-rearing, release and survival of african penguin chicks abandoned before independence by moulting parents(Public Library of Science, 2014) Sherley, Richard B; Waller, Lauren J; Strauss, Venessa; Geldenhuys, Deon; Underhill, Les G; Parsons, Nola JThe African penguin Spheniscus demersus has an ‘Endangered’ conservation status and a decreasing population. Following abandonment, 841 African penguin chicks in 2006 and 481 in 2007 were admitted to SANCCOB (Southern African Foundation for the Conservation of Coastal Birds) for hand-rearing from colonies in the Western Cape, South Africa, after large numbers of breeding adults commenced moult with chicks still in the nest. Of those admitted, 91% and 73% respectively were released into the wild. There were veterinary concerns about avian malaria, airsacculitis and pneumonia, feather-loss and pododermatitis (bumblefoot). Post-release juvenile (0.32, s.e. = 0.08) and adult (0.76, s.e. = 0.10) survival rates were similar to African penguin chicks reared after oil spills and to recent survival rates recorded for naturally-reared birds. By December 2012, 12 birds had bred, six at their colony of origin, and the apparent recruitment rate was 0.11 (s.e. = 0.03). Hand-rearing of abandoned penguin chicks is recommended as a conservation tool to limit mortality and to bolster the population at specific colonies. The feasibility of conservation translocations for the creation of new colonies for this species using hand-reared chicks warrants investigation. Any such programme would be predicated on adequate disease surveillance programmes established to minimise the risk of disease introduction to wild birds.
- ItemOpen AccessHumoral immune responses to Pneumocystis jirovecii antigens in HIV-infected and uninfected young children with pneumocystis pneumonia(Public Library of Science, 2013) Djawe, Kpandja; Daly, Kieran R; Levin, Linda; Zar, Heather J; Walzer, Peter DBACKGROUND: Humoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood. METHODS: Consecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC) were analyzed. RESULTS: 149 children were enrolled of whom 96 (64%) were HIV-infected. PcP occurred in 69 (72%) of HIV-infected and 14 (26%) of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP. CONCLUSIONS: Young HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP.
- ItemOpen AccessLong-term use of Everolimus in patients with Tuberous Sclerosis Complex: final results from the EXIST-1 study(Public Library of Science, 2016) Franz, David N; Belousova, Elena; Sparagana, Steven; Bebin, E Martina; Frost, Michael D; Kuperman, Rachel; Witt, Olaf; Kohrman, Michael H; Flamini, J Robert; Wu, Joyce Y; Curatolo, Paolo; De Vries, Petrus J; Berkowitz, Noah; Niolat, Julie; Jóźwiak, SergiuszBACKGROUND: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations of tuberous sclerosis complex (TSC). However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828). Methods and FINDINGS: EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m 2 /day) titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point) was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years) who received ≥1 dose of everolimus (median duration, 47.1 months), 57.7% (95% confidence interval [CI], 47.9-67.0) achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2%) achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs) was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence) suspected to be treatment-related were stomatitis (43.2%) and mouth ulceration (32.4%). CONCLUSIONS: Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a significant proportion of patients. Trial Registration ClinicalTrials.gov NCT00789828
- ItemOpen AccessNiger's child survival success, contributing factors and challenges to sustainability: a retrospective analysis(Public Library of Science, 2016) Besada, Donela; Kerber, Kate; Leon, Natalie; Sanders, David; Daviaud, Emmanuelle; Rohde, Sarah; Rohde, Jon; Damme, Wim van; Kinney, Mary; Manda, Samuel; Oliphant, Nicholas P; Hachimou, Fatima; Ouedraogo, Adama; Ghali, Asma Yaroh; Doherty, TanyaBACKGROUND: Household surveys undertaken in Niger since 1998 have revealed steady declines in under-5 mortality which have placed the country 'on track' to reach the fourth Millennium Development goal (MDG). This paper explores Niger's mortality and health coverage data for children under-5 years of age up to 2012 to describe trends in high impact interventions and the resulting impact on childhood deaths averted. The sustainability of these trends are also considered. Methods and FINDINGS: Estimates of child mortality using the 2012 Demographic and Health Survey were developed and maternal and child health coverage indicators were calculated over four time periods. Child survival policies and programmes were documented through a review of documents and key informant interviews. The Lives Saved Tool (LiST) was used to estimate the number of child lives saved and identify which interventions had the largest impact on deaths averted. The national mortality rate in children under-5 decreased from 286 child deaths per 1000 live births (95% confidence interval 177 to 394) in the period 1989-1990 to 128 child deaths per 1000 live births in the period 2011-2012 (101 to 155), corresponding to an annual rate of decline of 3.6%, with significant declines taking place after 1998. Improvements in the coverage of maternal and child health interventions between 2006 and 2012 include one and four or more antenatal visits, maternal Fansidar and tetanus toxoid vaccination, measles and DPT3 vaccinations, early and exclusive breastfeeding, oral rehydration salts (ORS) and proportion of children sleeping under an insecticide-treated bed net (ITN). Approximately 26,000 deaths of children under-5 were averted in 2012 due to decreases in stunting rates (27%), increases in ORS (14%), the Hib vaccine (14%), and breastfeeding (11%). Increases in wasting and decreases in vitamin A supplementation negated some of those gains. Care seeking at the community level was responsible for an estimated 7,800 additional deaths averted in 2012. A major policy change occurred in 2006 enabling free health care provision for women and children, and in 2008 the establishment of a community health worker programme. CONCLUSION: Increases in access and coverage of care for mothers and children have averted a considerable number of childhood deaths. The 2006 free health care policy and health post expansion were paramount in reducing barriers to care. However the sustainability of this policy and health service provision is precarious in light of persistently high fertility rates, unpredictable GDP growth, a high dependence on donor support and increasing pressures on government funding.
- ItemOpen AccessPneumocystis jirovecii pneumonia in tropical and low and middle income countries: a systematic review and meta-regression(Public Library of Science, 2013) Lowe, David M; Rangaka, Molebogeng X; Gordon, Fabiana; James, Chris D; Miller, Robert FObjective: Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and low and middle income countries (LMIC). We sought to investigate predictors of PCP in these settings. Design Systematic review and meta-regression. METHODS: Meta-regression of predictors of PCP diagnosis (33 studies). Qualitative and quantitative assessment of recorded CD4 counts, receipt of prophylaxis and antiretrovirals, sensitivity and specificity of clinical signs and symptoms for PCP, co-infection with other pathogens, and case fatality (117 studies). RESULTS: The most significant predictor of PCP was per capita Gross Domestic Product, which showed strong linear association with odds of PCP diagnosis (p<0.0001). This was not explained by study design or diagnostic quality. Geographical area, population age, study setting and year of study also contributed to risk of PCP. Co-infection was common (444 episodes/1425 PCP cases), frequently with virulent organisms. The predictive value of symptoms, signs or simple tests in LMIC settings for diagnosis of PCP was poor. Case fatality was >30%; treatment was largely appropriate. Prophylaxis appeared to reduce the risk for development of PCP, however 24% of children with PCP were receiving prophylaxis. CD4 counts at presentation with PCP were usually <200×10 3/ ml. CONCLUSIONS: There is a positive relationship between GDP and risk of PCP diagnosis. Although failure to diagnose infection in poorer countries may contribute to this, we also hypothesise that poverty exposes at-risk patients to a wide range of infections and that the relatively non-pathogenic P. jirovecii is therefore under-represented. As LMIC develop economically they eliminate the conditions underlying transmission of virulent infection: P. jirovecii , ubiquitous in all settings, then becomes a greater relative threat.
- ItemOpen AccessSevere community-acquired pneumonia(1996) Potgieter, Peter Daniel; Linton, DavidIn this thesis I will review the current knowledge of community-acquired pneumonia, including its classification, pathogenesis, pathology, aetiology, diagnosis, and antibiotic therapy and report my experience with severe community-acquired pneumonia in patients requiring admission to our respiratory intensive care unit. The original research in this thesis comprises a prospective, descriptive analysis of 196 cases of severe community-acquired pneumonia requiring admission to the Respiratory Intensive Unit at Groote Schuur Hospital from January 1987 until December 1992, with emphasis on the influence of aetiology on the severity of pneumonia, the· aetiological diagnosis of pneumonia in severely ill patients, measures of severity of pneumonia, and an audit of ICU therapy and outcome. In addition, different aspects of novel therapies and specific aetiological varieties of pneumonia which have been investigated over the past ten years will be presented.
- ItemOpen AccessSevere community-acquired pneumonia(1996) Potgieter, Peter Daniel
- ItemOpen AccessStreptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008(Public Library of Science, 2015) Cohen, Cheryl; Naidoo, Nireshni; Meiring, Susan; de Gouveia, Linda; van Mollendorf, Claire; Walaza, Sibongile; Naicker, Preneshni; Madhi, Shabir A; Feldman, Charles; Klugman, Keith P; Dawood, Halima; von Gottberg, Anne; GERMS-SABACKGROUND: An association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa. METHODS: IPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003-2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent. RESULTS: Among 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1-3.5) and 19F (OR 2.9, 95%CI 1.4-6.1) vs. serotype 4; increasing age (25-44 years, OR 1.8, 95%CI 1.0-3.0; 45-64 years, OR 3.6, 95%CI 2.0-6.4; ≥65 years, OR 5.2, 95%CI 1.9-14.1; vs. 15-24 years); meningitis (OR 4.1, 95%CI 3.0-5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0-2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases. CONCLUSION: Mortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.
- ItemOpen AccessTranscriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers(Public Library of Science, 2013) Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, YvonneRationale: New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives: To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods: We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results: An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions: Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.