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PloS One 2015To evaluate risk factors for death from acute lower respiratory infections (ALRI) in children in low- and middle-income countries. (Meta-Analysis)
Meta-Analysis Review
Risk factors for mortality from acute lower respiratory infections (ALRI) in children under five years of age in low and middle-income countries: a systematic review and meta-analysis of observational studies.
OBJECTIVE
To evaluate risk factors for death from acute lower respiratory infections (ALRI) in children in low- and middle-income countries.
DESIGN
Systematic review and meta-analysis.
STUDY SELECTION
Observational studies reporting on risk factors for death from ALRI in children below five years in low- and middle income countries.
DATA SOURCES
Medline, Embase, Global Health Library, Lilacs, and Web of Science to January 2014.
RISK OF BIAS ASSESSMENT
Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger's test to evaluate publication bias.
RESULTS
Out of 10,655 papers retrieved, 77 studies from 39 countries (198,359 children) met the inclusion criteria. Host and disease characteristics more strongly associated with ALRI mortality were: diagnosis of very severe pneumonia as per WHO definition (odds ratio 9.42, 95% confidence interval 6.37‒13.92); age below two months (5.22, 1.70‒16.03); diagnosis of Pneumocystis Carinii (4.79, 2.67‒8.61), chronic underlying diseases (4.76, 3.27‒6.93); HIV/AIDS (4.68, 3.72‒5.90); and severe malnutrition (OR 4.27, 3.47‒5.25). Socio-economic and environmental factors significantly associated with increased odds of death from ALRI were: young maternal age (1.84, 1.03‒3.31); low maternal education (1.43, 1.13‒1.82); low socio-economic status (1.62, 1.32‒2.00); second-hand smoke exposure (1.52, 1.20 to 1.93); indoor air pollution (3.02, 2.11‒4.31). Immunisation (0.46, 0.36‒0.58) and good antenatal practices (0.50, 0.31‒0.81) were associated with decreased odds of death.
CONCLUSIONS
Host and disease characteristics as well as socio-economic and environmental determinants affect the risk of death from ALRI in children. Together with the prevention and treatment of chronic diseases, interventions to modify underlying risk factors such as poverty, lack of female education, and poor environmental conditions, should be considered among the strategies to reduce ALRI mortality in children in low- and middle-income countries.
Topics: Child, Preschool; Developing Countries; Environmental Exposure; Humans; Infant; Infant, Newborn; Observational Studies as Topic; Poverty; Respiratory Tract Infections; Risk Factors; Survival Analysis
PubMed: 25635911
DOI: 10.1371/journal.pone.0116380 -
Transplantation Proceedings Nov 2014Pneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients. (Review)
Review
BACKGROUND
Pneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients.
METHODS
We searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms "liver transplantation" and "pneumocystis." Our search yielded 60 articles, 35 of which were used for our review.
RESULTS
P. jirovecii pneumonia (PJP) has an incidence of 1%-11% in liver transplant recipients without prophylaxis and mortality rates of 7%-88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%-3%. The duration of its use varies from 3 months to 1 year after the liver transplantation.
CONCLUSIONS
PJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.
Topics: Anti-Bacterial Agents; Global Health; Humans; Immunocompromised Host; Incidence; Liver Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Transplant Recipients
PubMed: 25420860
DOI: 10.1016/j.transproceed.2014.09.156 -
The Brazilian Journal of Infectious... 2014The natural history of HIV infection has changed dramatically after the introduction of highly active antiretroviral therapy. Currently, opportunistic illnesses still... (Review)
Review
Trends in overall opportunistic illnesses, Pneumocystis carinii pneumonia, cerebral toxoplasmosis and Mycobacterium avium complex incidence rates over the 30 years of the HIV epidemic: a systematic review.
BACKGROUND
The natural history of HIV infection has changed dramatically after the introduction of highly active antiretroviral therapy. Currently, opportunistic illnesses still represent a major cause of death and hospitalization in this population. In this study, we review the trends in opportunistic illnesses incidence rates and compare the results observed in high-income settings with that for low/middle-income settings, with special attention given to studies from Brazil.
METHODS
We systematically searched Pubmed, Web of Science, Lilacs and Google scholar for publications on HIV associated opportunistic illness. Studies reporting rates based on person-time for all opportunistic illnesses and/or the three opportunistic infections of interest, namely, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacterium avium complex were included.
RESULTS
Significant reductions in the incidence rates were demonstrated for opportunistic illnesses overall and also for the specific opportunistic infections included in the present study, both in high and low/middle-income settings. Out of the 37 studies included in the present review, almost 70% were from high-income settings. All the studies conducted in low/middle-income settings were single center studies and four were from Brazil. We found no study from Brazil reporting annual incidence rates of opportunistic illnesses.
CONCLUSIONS
Opportunistic illnesses remain an important public health problem. To better guide health policies in low/middle-income settings, multicenter cohort studies should be encouraged. Studies from Brazil are urgently needed to assess the current burden of opportunistic illnesses in our population and to support the planning of HIV/AIDS health care services organization.
Topics: AIDS-Related Opportunistic Infections; Epidemics; Humans; Mycobacterium avium-intracellulare Infection; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral
PubMed: 24275372
DOI: 10.1016/j.bjid.2013.10.003 -
PloS One 2013As a promising tool, PCR in bronchoalveolar lavage fluid (BALF) has not been accepted as a diagnostic criterion for PJP. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
As a promising tool, PCR in bronchoalveolar lavage fluid (BALF) has not been accepted as a diagnostic criterion for PJP.
OBJECTIVE
We undertook a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays in BALF for PJP.
METHODS
Eligible studies from PubMed, Embase and Web of Science reporting PCR assays in BALF for diagnosing PJP were identified. A bivariate meta-analysis of the method's sensitivity, specificity, and positive and negative likelihood ratios with a 95% confidence interval (CI) were analyzed. The post-test probability was performed to evaluate clinical usefulness. A summary receiver operating characteristics (SROC) curve was used to evaluate overall performance. Subgroup analyses were carried out to analysis the potential heterogeneity.
RESULTS
Sixteen studies published between 1994 and 2012 were included. The summary sensitivity and specificity values (95% CI) of PCR in BALF for diagnosis of PJP were 98.3% (91.3%-99.7%) and 91.0% (82.7%-95.5%), respectively. The positive and negative likelihood ratios were 10.894 (5.569-21.309) and 0.018 (0.003-0.099), respectively. In a setting of 20% prevalence of PJP, the probability of PJP would be over 3-fold if the BALF-PCR test was positive, and the probability of PJP would be less than 0.5% if it was negative. The area under the SROC curve was 0.98 (0.97-0.99).
CONCLUSIONS
The method of PCR in BALF shows high sensitivity and good specificity for the diagnosis of PJP. However, clinical practice for the diagnosis of PJP should consider the consistent respiratory symptoms, radiographic changes and laboratory findings of the suspected patients.
Topics: Analysis of Variance; Bronchoalveolar Lavage Fluid; Clinical Trials as Topic; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction
PubMed: 24023814
DOI: 10.1371/journal.pone.0073099 -
PloS One 2013Pneumocystis jirovecii pneumonia (PCP), the commonest opportunistic infection in HIV-infected patients in the developed world, is less commonly described in tropical and... (Review)
Review
OBJECTIVE
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.
Topics: Developing Countries; Humans; Meta-Analysis as Topic; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 23936365
DOI: 10.1371/journal.pone.0069969 -
BMC Medicine Jan 2013Smoking is common in people infected with HIV but cessation support is not a routine part of clinical care. The aim was to assess whether smoking is a risk factor for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Smoking is common in people infected with HIV but cessation support is not a routine part of clinical care. The aim was to assess whether smoking is a risk factor for pneumonia in people with HIV and whether smoking cessation ameliorates excess risk.
METHODS
We performed MEDLINE and Embase database searches and included cohort or case-control studies conducted in adult patients infected with HIV extracting a hazard ratio (HR) or odds ratio (OR) that compared the incidence of bacterial pneumonia or pneumonia caused by Pneumocystis jiroveci (PCP) between two smoking categories. Studies were appraised for quality and combined using inverse variance meta-analysis.
RESULTS
Fourteen cohort and case-control studies were included. Assessment of outcome was good, but assessment of exposure status was poor. Current smokers were at higher risk of bacterial pneumonia than former smokers: HR 1.37 (95% confidence interval (CI): 1.06, 1.78). There was no evidence that former smokers were at higher risk than never smokers: HR 1.24 (95%CI: 0.96, 1.60). Current smokers were at higher risk of bacterial pneumonia than current non-smokers: HR of 1.73 (95%CI: 1.44, 2.06). There was no evidence that smoking increased the incidence of PCP. The HR for current versus non-smokers was 0.94 (95%CI: 0.79, 1.12), but from case-control studies the OR was 1.76 (95%CI: 1.25, 2.48) with heterogeneity. Confined to higher quality studies, the OR was 0.97 (95%CI: 0.81, 1.16). Residual confounding is possible, but available data suggest this is not an adequate explanation.
CONCLUSIONS
Smoking is a risk factor for bacterial pneumonia but not PCP and smoking cessation reduces this risk.See related article: http://www.biomedcentral.com/1741-7015/11/16.
Topics: HIV Infections; Humans; Incidence; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Smoking Cessation
PubMed: 23339513
DOI: 10.1186/1741-7015-11-15 -
PloS One 2011HIV viral load (VL) is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP) prophylaxis discontinuation, but suppression of plasma viremia with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV viral load (VL) is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP) prophylaxis discontinuation, but suppression of plasma viremia with antiretroviral therapy may allow for discontinuation of PCP prophylaxis even with CD4 count <200 cells/µL.
METHODS
A systematic review was performed to determine the incidence of PCP in HIV-infected individuals with CD4 count <200 cells/µL and fully suppressed VL on antiretroviral therapy but not receiving PCP prophylaxis.
RESULTS
Four articles examined individuals who discontinued PCP prophylaxis with CD4 count <200 cells/µL in the context of fully suppressed VL on antiretroviral therapy. The overall incidence of PCP was 0.48 cases per 100 person-years (PY) (95% confidence interval (CI) (0.06-0.89). This was lower than the incidence of PCP in untreated HIV infection (5.30 cases/100 PY, 95% CI 4.1-6.8) and lower than the incidence in persons with CD4 count <200 cells/µL, before the availability of highly active antiretroviral therapy (HAART), who continued prophylaxis (4.85/100 PY, 95% CI 0.92-8.78). In one study in which individuals were stratified according to CD4 count <200 cells/µL, there was a greater risk of PCP with CD4 count ≤100 cells/µL compared to 101-200 cells/µL.
CONCLUSION
Primary PCP prophylaxis may be safely discontinued in HIV-infected individuals with CD4 count between 101-200 cells/µL provided the VL is fully suppressed on antiretroviral therapy. However, there are inadequate data available to make this recommendation when the CD4 count is ≤100 cells/µL. A revision of guidelines on primary PCP prophylaxis to include consideration of the VL is merited.
Topics: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; HIV Infections; Humans; Incidence; Pneumocystis carinii; Pneumonia, Pneumocystis; Viral Load
PubMed: 22194853
DOI: 10.1371/journal.pone.0028570 -
Journal of Clinical Microbiology Jan 2012Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted... (Meta-Analysis)
Meta-Analysis Review
Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP.
Topics: Aspergillosis; Candidiasis, Invasive; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Proteoglycans; ROC Curve; Sensitivity and Specificity; Serum; beta-Glucans
PubMed: 22075593
DOI: 10.1128/JCM.05267-11 -
The Pediatric Infectious Disease Journal Oct 2011Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected children. (Review)
Review
BACKGROUND
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected children.
OBJECTIVES AND METHODS
A systematic review of studies that were published between January 1990 and February 2009 on the etiology and antimicrobial or adjunctive systemic management of CAP in HIV-infected children.
RESULTS
Pneumocystis jirovecii had the strongest association with HIV infection, with a summary odds ratio of 10.1 (95% confidence interval [CI], 17.7-62.1) and 9.1 (95% CI, 2.5-33.1) in antemortem and postmortem studies, respectively. Cytomegalovirus was strongly associated with HIV positivity among fatal cases of pneumonia (summary odds ratio = 14.4 [95% CI, 6.7-30.8]). There was a trend toward a greater prevalence of Staphylococcus aureus (odds ratio, 2.5; 95% CI, 0.95-6.4) in HIV-infected children. Major limitations identified included substantial methodological heterogeneity across studies, limited sensitivity of assays for diagnosing bacterial pneumonia, and studies primarily being undertaken in the absence of antiretroviral treatment or cotrimoxazole prophylaxis. No a priori-planned randomized controlled trials on antimicrobial management of CAP in HIV-infected children were identified.
CONCLUSIONS
A World Health Organization panel used this review as well as analysis of risks and benefits to revise recommendations for antimicrobial treatment of CAP. Ampicillin plus gentamicin or ceftriaxone is now recommended as first-line empiric regimens for treating severe and very severe CAP in HIV-infected children. In addition, treatment with cloxacillin or vancomycin is recommended in settings with a high incidence of methicillin-resistant S. aureus, and particularly if clinical or microbiological evidence of S. aureus pneumonia exist. Further studies in HIV-infected children on CAP etiology and antibiotic treatment are required in the era of antiretroviral treatment.
Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Community-Acquired Infections; Cytomegalovirus; HIV Infections; Humans; Infant; Infant, Newborn; Pneumocystis carinii; Pneumonia; Prevalence; Staphylococcus aureus
PubMed: 21857264
DOI: 10.1097/INF.0b013e31822d989c -
Revista Iberoamericana de Micologia Mar 2009Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Although several new antifungal agents have been... (Review)
Review
BACKGROUND
Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Although several new antifungal agents have been developed in the past few years, the management of serious fungal infections continues to be problematic.
AIMS
To review the pharmacodynamics and pharmacokinetics of a new antifungal agent: micafungin.
METHODS
A systematic review of biomedic databases (EBSCO Open Journals, Ovid Online, Proquest Medical Library, PubMed/Medline, Science Direct, Springer Links and Wiley Interscience) has been performed. Search was conducted from 2000 to 2008. Supplementary sources included abstracts from the Interscience Conference on Antimicrobial Agents (ICAAC) and Chemotherapy and the Infectious Diseases Society of America (IDSA) from 1998 to 2008.
RESULTS
Micafungin has a potent mechanism of action: inhibits beta-1,3-D-glucan synthase interfering with fungal cell wall synthesis. This agent shares with caspofungin an identical spectrum of in vitro activity against Candida albicans, non-albicans Candida species, and Aspergillus. Due to the limited oral availability, micafungin is available for parenteral administration only. Micafungin is characterized by a linear pharmacokinetic profile and substantially fewer toxic effects. Micafungin is a poor substrate for the cytochrome P450 enzymes, and compared to azoles, fewer drug interactions have been described. No dose reduction is required in renal impairment or in mild to moderate liver failure.
CONCLUSIONS
The pharmacodynamic and pharmacokinetic profiles of micafungin imply that this drug is a safe alternative for the treatment of fungal infections. Micafungin can be safely co-administered with most drugs without the need for dosage adaptation even in patients with renal o liver function impairment.
Topics: Adolescent; Adult; Aged; Animals; Antifungal Agents; Aspergillus; Biotransformation; Candida; Child; Child, Preschool; Drug Evaluation, Preclinical; Drug Interactions; Echinocandins; Fungal Proteins; Glucosyltransferases; Humans; Infant, Newborn; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Middle Aged; Molecular Structure; Mycoses; Pneumocystis carinii; Young Adult
PubMed: 19463274
DOI: 10.1016/S1130-1406(09)70005-1